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MyDeficiencies

Zafirlukast

cysteinyl leukotriene receptor 1 (CysLT1) antagonist

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Zafirlukast has no classical nutrient-depletion machinery, and its label says nothing about vitamins, minerals or supplements. The only nutrition statement is a timing interaction running from food to drug: food lowers mean zafirlukast bioavailability by about 40%, so the label advises dosing at least 1 hour before or 2 hours after meals [1]. That is a nutrient-to-drug absorption interaction (Hard Rule 4), not a depletion, and it is handled in the monitoring panel. The drug is extensively metabolized by CYP2C9 and is eliminated mainly in bile, with about 10% of a dose in urine; it inhibits CYP2C9 and CYP3A4 in vitro, and raised S-warfarin AUC by 63% with a prothrombin time rise of about 35% [1]. Those findings are drug-drug effects. They are not vitamin K findings, and no vitamin K measurement was found.

cysteinyl leukotriene receptor 1 (CysLT1) antagonist · ATC R03DC01 (WHO code as listed on Wikipedia [2]) · also sold as Accolate (US original); generic tablets · reviewed 2026-10-07. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Zafirlukast in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low
Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

Folate: transporter inhibition and redistribution, mouse and in vitro only

Yellow — Low

See study details

Zafirlukast inhibits the folate transporters SLC19A1 and SLC46A1 in vitro and, in mice, co-dosing raised plasma folic acid exposure and lowered hepatic folic acid accumulation; no human folate measurement exists.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: None located. No study of folate status in zafirlukast users was found. Only one in vivo folic acid result is on record, from mice [5].
  • At-risk subgroups: None established. The authors suggest caution with antifolates such as methotrexate and pemetrexed, but their abstract reports no in vivo antifolate data. Treat as a research signal for transporter-mediated drug interactions.

Direction

Transport inhibition with redistribution. Plasma exposure went up and liver accumulation went down in mice. Neither a human depletion nor an excess has been shown. Do not read this as either a reason to raise or to lower folate intake.

Regulatory status

Not mentioned in the zafirlukast label [1].

Population evidence

No human data. Luo et al. 2026 [5] (Chemico-Biological Interactions 439:112345; PMID 42716456) tested four leukotriene receptor antagonists (MK571, montelukast, zafirlukast, pranlukast) against folic acid, methotrexate and pemetrexed transport. Per a paraphrase of the PubMed abstract, all four reduced SLC19A1 and SLC46A1 transport in a concentration-dependent way: IC50 2.34 to 31.8 uM (SLC19A1) and 2.79 to 45.4 uM (SLC46A1); noncompetitive inhibition of SLC19A1 (Ki 5.09 to 6.71 uM) and uncompetitive inhibition of SLC46A1 (Ki 4.12 to 95.1 uM). These ranges are pooled across the four antagonists. Repair pass 2026-10-08: the PubMed single-record export was read a second time and the OpenAlex works/pmid record was checked (abstract field null; keywords include zafirlukast). The abstract contains no zafirlukast-specific IC50 or Ki and no zafirlukast-specific mouse numbers; its in vivo statement names montelukast and zafirlukast jointly. The full text was not opened (publisher page disallowed by robots rules), so the zafirlukast-specific values remain unretrieved and may exist only in the paper's tables. In mice, co-administering montelukast or zafirlukast with folic acid raised folic acid AUC and Cmax, lengthened its half-life and decreased hepatic accumulation. Mouse doses, sample size and the size of the AUC change were not in the abstract text I could see. The OpenAlex keyword list for the record includes zafirlukast [5].

Mechanism

Named: direct inhibition of two folate transporters (reduced folate carrier SLC19A1; proton-coupled folate transporter SLC46A1). Whether free drug concentrations in people reach the micromolar range is not established here. Zafirlukast is over 99% protein bound [1], which lowers free concentration; that is my inference and was not tested in the paper.

Cohort test

Zafirlukast was named in the studied system (cell transport assays and mouse), so this is Tier B for zafirlukast, not class extrapolation. Montelukast and the other antagonists in the same paper were not borrowed to support a zafirlukast result.

Counter-evidence held on record

Counter-evidence and confounding The paper is a 2026 laboratory study read only as a paraphrase of its PubMed abstract, twice (full text behind a publisher site that blocks automated reading). It is also a laboratory source, so it cannot reach orange (which needs a human Tier A cohort) however large the effect. No second independent source exists. Pooled ranges hide how potent zafirlukast is by itself. Any folate change in people would need an independent human study to rule out confounding by diet and indication. Framing caution This is a transporter-interaction research signal, not a folate deficiency claim and not an excess claim. It does not support taking or avoiding folic acid. Make no folate dosing recommendation from this entry.

Vitamin K

Not graded — disclosed evidence gap

See study details

No evidence on zafirlukast and vitamin K status was retrieved. The warfarin prothrombin time rise is a drug-drug effect.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C evidence on vitamin K and no circulating claim of vitamin K depletion found. The prothrombin time rise and bleeding reports are outcomes of a CYP2C9 interaction and must not be filed as vitamin K deficiency (Hard Rules 2 and 4). This is a disclosed gap, not reassurance. The warfarin interaction is in the monitoring panel.

What was searched

PubMed search listing "zafirlukast warfarin" (9 records) and the compound query "zafirlukast" with vitamin D, vitamin K, vitamin B12, folate, selenium, zinc (3 records, none on vitamin K). Label read.

Channel outcomes

None of the 9 warfarin records reported vitamin K status or vitamin K-dependent clotting factor data. The prothrombin time rise is attributed to CYP2C9 inhibition raising S-warfarin exposure (AUC +63%) [1][12]. The label also lists postmarketing bleeding or bruising [1]. Europe PMC and Semantic Scholar rate-limited. Repair pass 2026-10-08: a web search for zafirlukast with warfarin, prothrombin time and vitamin K-dependent clotting factors returned generic warfarin pages and a drug-interaction listing (hellopharmacist.com, not opened); no zafirlukast vitamin K or PIVKA record was surfaced, and a PubMed phrasing aimed at PIVKA or vitamin K was not run because of 429 responses. Likely genuine gap.

Vitamin D

Not graded — disclosed evidence gap

See study details

No evidence on zafirlukast and vitamin D status or bone was retrieved.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met on what was retrieved: no Tier B or C source and no circulating claim found. A disclosed gap and partly tooling-limited; a fuller re-check (vitamin D, 25-hydroxyvitamin D, bone density) is warranted.

What was searched

PubMed compound query: zafirlukast with "vitamin D", "vitamin K", "vitamin B12", folate, selenium, zinc (3 records, none on vitamin D). Label and Drugs.com, PubChem, Wikipedia pages read for nutrient statements.

Channel outcomes

No vitamin D record. A dedicated vitamin D query and bone mineral density, calcium or fracture queries were not run separately because of rate limiting, so this is the most tooling-limited ungraded entry. Europe PMC and Semantic Scholar rate-limited. Repair pass 2026-10-08: three separate PubMed listings (zafirlukast with bone density; with vitamin D; with osteoporosis, bone mineral density or vitamin D) were each rejected by the fetch proxy with HTTP 429 after waits of 2 to 5 minutes, and an OpenAlex works search was also 429. A web search for zafirlukast with bone mineral density, vitamin D, calcium or osteoporosis returned only unrelated osteoporosis papers (denosumab, Cochrane) with no zafirlukast record. The bone, calcium and 25-hydroxyvitamin D queries therefore remain unrun on PubMed.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden: reverse direction, with one mixed in vitro signal

Yellow — Low

See study details

Zafirlukast increased mitochondrial respiration and biogenesis in human bronchial epithelial cells and preserved membrane potential in toxin-exposed hepatocytes, while one cancer-cell study describes mitochondria-mediated apoptosis; no human mitochondrial-toxicity data exist.

Full detail, limits and 4 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: No study of mitochondrial toxicity of zafirlukast in primary human hepatocytes or in patients was located. The retrieved evidence does not explain the label's hepatotoxicity warning.
  • At-risk subgroups: Not established. Women appear over-represented in the hepatotoxicity reports per a secondary source [2]; that is an outcome, not a mitochondrial finding.

Direction

Mostly reverse (protective or stimulatory) in normal-type cells; pro-apoptotic mitochondrial effect reported in hepatocellular carcinoma cells. No evidence of mitochondrial damage by zafirlukast in non-cancer cells in the records read.

Regulatory status

The label reports hepatotoxicity but no mitochondrial mechanism [1].

Population evidence

No human data. J Mol Histol 2021 [6] (PMID 33977464): in human bronchial epithelial cells, zafirlukast raised oxygen consumption, mitochondrial mass and mitochondrial DNA content and increased PGC-1alpha, NRF1 and TFAM, CREB-dependent (paraphrased abstract; concentrations not retrieved). Bioengineered 2021 [7] (PMID 34787067): in docetaxel-exposed LO-2 hepatocytes, zafirlukast preserved mitochondrial membrane potential and ATP and reduced caspase activity. Regul Toxicol Pharmacol 2019 [10] (PMID 31605713): title reports antineoplastic activity against hepatocellular carcinoma via mitochondria-mediated apoptosis; only a title and one excerpt line were seen.

Mechanism

Named for the reverse findings: CREB-PGC-1alpha biogenesis signaling [6] and SIRT1-NLRP3 [7]. For the apoptosis finding the details were not read.

Cohort test

Zafirlukast was the tested agent in all three records: Tier B. No class extrapolation.

Counter-evidence held on record

Counter-evidence and confounding In vitro concentrations were not compared with clinical exposures, and the pro-apoptotic finding in cancer cells likely reflects high-concentration anticancer pharmacology. Hepatotoxicity is an adverse outcome and must not be rewritten as mitochondrial burden without a measured link. Framing caution Do not describe this as mitochondrial damage or mitochondrial support in patients. It is a laboratory observation only.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress: reverse direction, cell and animal data

Yellow — Low

See study details

In human neutrophils, endothelial and renal cells in vitro, and in fish, zafirlukast lowered reactive oxygen species; no study shows zafirlukast raising systemic oxidative stress in people.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: None located. No study reporting a rise in oxidative markers with zafirlukast in non-diseased cells was found in the listing. A secondary web source says the drug's liver injury may involve a metabolic intermediate [2]; that is Tier D, unverified, and no oxidative-stress measurement supports it.
  • At-risk subgroups: None established.

Direction

Reverse (apparently protective). No redox-burden or antioxidant-depletion finding.

Regulatory status

No oxidative-stress statement in the label [1].

Population evidence

No human in vivo marker study. A PubMed listing for zafirlukast with reactive oxygen species [9] shows: human polymorphonuclear neutrophils from asthma patients and healthy volunteers exposed in vitro, with dose-dependent suppression of ROS and a higher dose needed in asthma cells (Curr Ther Res 2005, PMID 24672130); lower ROS in TNF-alpha-stimulated cultured endothelial cells (Biomed Pharmacother 2019, PMID 30594784); lower ROS, cytokines and apoptosis in rat renal mesangial cells exposed to advanced glycation end-products (Med Sci Monit 2019, PMID 31745068); lower ROS and aggregated proteins in ARPE-19 retinal cells (Sci Rep 2023, PMID 37580467); lower ROS or oxidative burst in Nile tilapia (2022, 2024). Also, zafirlukast reduced oxidative DNA damage in docetaxel-exposed human LO-2 hepatocytes [7]. Only listing-level or paraphrased summaries were read; no concentrations were retrieved, so relevance to clinical plasma levels is unknown.

Mechanism

Named at cell level: CysLT1 antagonism with p38 and NF-kB suppression in endothelial cells [9]; SIRT1-linked suppression of NLRP3 inflammasome activation in hepatocytes [7]. Direct radical scavenging by zafirlukast was not tested in the records read.

Cohort test

Zafirlukast itself was the tested agent in every record, so these are Tier B for this drug. No class extrapolation.

Counter-evidence held on record

Counter-evidence and confounding All data are cell, animal or ex vivo and concentrations were not compared with human plasma levels. A reverse-direction cell finding does not show antioxidant benefit in patients. Hepatotoxicity is a documented clinical outcome of the drug [1] and is not entered as oxidative stress. Framing caution This is a reverse-direction mechanistic note. It is not an antioxidant benefit claim and gives no basis for antioxidant supplementation.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Copper

Not graded — disclosed evidence gap

See study details

No evidence on zafirlukast and copper status was retrieved.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C source was found, and no circulating consumer claim about zafirlukast and copper was found on the pages reached. This is a disclosed gap, not a finding of safety. Re-check when search access is restored.

What was searched

PubMed search listing, query "zafirlukast copper" (export format). The label read (via summarizing fetch) and the Drugs.com and PubChem pages carry no copper statement.

Channel outcomes

The PubMed copper query returned an HTTP 404 page, which I read as zero matches (not confirmed against a second host). Europe PMC, Semantic Scholar and OpenAlex searches were rate-limited (HTTP 429) and could not be used for a second pass. Web search was unavailable (budget exhausted). Repair pass 2026-10-08: no new copper query could be opened (see the access note); ceruloplasmin and serum copper surrogate phrasings were planned but not run. Mixed result: likely a genuine gap, with a tooling-limited second check.

Iron

Not graded — disclosed evidence gap

See study details

No evidence on zafirlukast and iron status was retrieved.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C source and no circulating claim found. A disclosed gap, not reassurance. The label's postmarketing agranulocytosis and bleeding or bruising reports [1] are hematologic adverse events, not iron findings, and are not used.

What was searched

PubMed search listings: "zafirlukast iron" and "zafirlukast anemia" (the first was rate-limited twice and returned on a later retry). The label has no iron statement.

Channel outcomes

Both queries returned HTTP 404 pages, read as zero matches. A combined iron, hemoglobin, hemolysis, methemoglobin query was rate-limited and not rerun in that form. Europe PMC and Semantic Scholar rate-limited. Repair pass 2026-10-08: a PubMed listing for "zafirlukast methemoglobin" returned HTTP 404 (read as zero matches); ferritin and serum iron phrasings were planned but PubMed then returned HTTP 429 on every later attempt. A web search for zafirlukast with methemoglobinemia, hemolysis or hemolytic anemia returned only consumer drug pages and unrelated rasburicase records. Mixed result, likely genuine gap.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk: in vitro antibacterial data in non-gut species

Yellow — Low

See study details

Zafirlukast has in vitro antibacterial activity against Streptococcus agalactiae (respiration) and is a lead structure against Porphyromonas gingivalis; whether it changes the human gut microbiome has not been studied.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: Searches with the terms microbiota and dysbiosis returned only the two records above; no human or animal gut study appeared.
  • At-risk subgroups: None established.

Direction

Potential suppression of susceptible bacteria; direction in the gut is unknown.

Regulatory status

The label lists diarrhea (2.8% vs 2.1% placebo) and nausea (3.1% vs 2.0%) as common adverse events [1]. These are not microbiome measurements.

Population evidence

No fecal, 16S or metagenomic study of zafirlukast users was located. mBio 2018 [8]: zafirlukast inhibited aerobic respiration in S. agalactiae in vitro. ACS Med Chem Lett 2020 [11] (PMID 33062172): the title describes a second generation of zafirlukast derivatives with improved activity against P. gingivalis, which implies activity of the parent structure; the abstract text was seen only as a one-line summary, and no minimum inhibitory concentrations were retrieved.

Mechanism

Plausible for bacterial respiration targets (NDH-2). Whether intestinal commensals are susceptible, and whether biliary excretion (the main elimination route [1]) exposes the colon to active drug, was not studied in the records read.

Cohort test

Zafirlukast was the tested agent: Tier B, in non-gut species. Not class extrapolation.

Counter-evidence held on record

Counter-evidence and confounding Antibacterial activity in a screen is not a microbiome effect. Both organisms are not representative of the gut community, and no concentration at the colonic site is known. The weakest yellow in this dossier. Framing caution This is a theoretical flag only. Do not tell readers zafirlukast disrupts gut bacteria, and do not suggest probiotics from this entry.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

ATP production: preserved in toxin-exposed hepatocytes; bacterial respiration inhibited

Yellow — Low

See study details

Zafirlukast preserved ATP in docetaxel-exposed human hepatocytes in vitro, and separately inhibited NADH dehydrogenase-2 and aerobic respiration in Streptococcus agalactiae; no human ATP data exist.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: No human or animal measurement of tissue ATP after zafirlukast was located.
  • At-risk subgroups: None established.

Direction

Reverse (preserved ATP) in mammalian cells. Inhibitory in one bacterial species, where respiration is the target and not a human energy deficit.

Regulatory status

No energy-metabolism statement in the label [1].

Population evidence

No human data. Bioengineered 2021 [7]: LO-2 hepatocytes, docetaxel injury; zafirlukast raised ATP and membrane potential. mBio 2018 [8] (PMID 29970468): drug screen found zafirlukast inhibited NDH-2 activity and aerobic respiration in intact S. agalactiae (the mouse model in that paper tested NDH-2 gene loss, not zafirlukast). A PubMed listing for zafirlukast with ATP [13] returned other records where ATP appeared only as an ABC transporter or viral helicase context (ABCG2, MRP2, MRP1 efflux inhibition, Langat helicase docking); these are not ATP-production findings and were not used.

Mechanism

Named for the hepatocyte result (SIRT1-NLRP3, upstream of mitochondrial protection) [7]; for the bacterial result, inhibition of a type 2 NADH dehydrogenase that has no direct counterpart in human mitochondria (my inference from the title; human complex I was not tested).

Cohort test

Zafirlukast was the studied drug in both records: Tier B. No class extrapolation.

Counter-evidence held on record

Counter-evidence and confounding The hepatocyte ATP finding is the same record used for oxidative stress and mitochondrial burden (see Overlap map) and is a rescue effect under a toxin, not a baseline change. Abstracts were read only as summaries. Framing caution This is not a low-energy or fatigue claim. It gives no basis for energy supplements.

Oxygen delivery/utilization

Not graded — disclosed evidence gap

See study details

No evidence on zafirlukast and hemoglobin, red-cell mass or tissue oxygen delivery was retrieved.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C source and no circulating claim found. The drug's intended bronchodilatory or anti-inflammatory effect is not an oxygen-delivery finding and is not entered (Hard Rule 2). This is a disclosed gap, not reassurance.

What was searched

PubMed search listings: "zafirlukast hemoglobin" and "zafirlukast anemia". The label's adverse-event list was read for hematologic content.

Channel outcomes

Both queries returned HTTP 404 pages, read as zero matches. Repair pass 2026-10-08: "zafirlukast methemoglobin" returned HTTP 404 on PubMed (read as zero matches, not confirmed on a second host); "zafirlukast hemolysis" was rate-limited (HTTP 429) and could not be read, so hemolysis remains unqueried on PubMed. A web search for zafirlukast with methemoglobinemia, hemolysis or hemolytic anemia surfaced no zafirlukast-specific record (only consumer drug pages and an unrelated rasburicase case). Label hematologic content is limited to postmarketing agranulocytosis and bleeding or bruising [1]. Mixed result, likely genuine gap with an incomplete surrogate-endpoint sweep.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • Any zafirlukast-specific nutrient depletion claim

    Where it comes from: None found. Pages reached: Drugs.com food interactions [4], PubChem [3], Wikipedia [2]. Depletion-handbook and retailer pages were not reached (web search unavailable).

    Why it fails: Drugs.com lists one food interaction (take on an empty stomach) and no vitamin, mineral or depletion claim [4]. The claim audit is incomplete for the reason stated; absence of a located claim is not evidence that none circulates.

  • Food effect read as a nutrient depletion (hazard)

    Where it comes from: Not a located claim. The label's 40% bioavailability reduction with food [1].

    Why it fails: The direction is food reducing drug absorption, a timing interaction (Hard Rule 4). Zafirlukast does not deplete any nutrient through this mechanism.

  • Prothrombin time rise read as vitamin K depletion (hazard)

    Where it comes from: Not a located claim. The label's warfarin interaction (S-warfarin AUC +63%, PT +35%) [1].

    Why it fails: The label attributes it to CYP2C9 inhibition raising warfarin exposure. No vitamin K measurement exists, and an INR change is an outcome (Hard Rule 2).

How the body handles this medication

Metabolism and enzymes
Extensively metabolized; hydroxylated metabolites form via CYP2C9. In vitro, zafirlukast inhibits CYP3A4 and CYP2C9 at concentrations near clinically achieved plasma levels. The label gives no CYP induction. S-warfarin AUC rose 63% and half-life 36%; prothrombin time rose about 35%.[1] DailyMed generic label, Clinical Pharmacology and Drug Interactions (via summarizing fetch). In vitro IC50 about 7.0 uM for tolbutamide hydroxylation and Ki about 5.86 uM for CYP2C9 in human liver microsomes [12].
Elimination
Biliary excretion is the main route; about 10% of a dose is excreted in urine and zafirlukast is not detected in urine. Mean plasma half-life about 8 to 16 hours.[1]
Absorption and food
Food reduces mean bioavailability by about 40%. Label instruction: take at least 1 hour before or 2 hours after meals. This is a nutrient-to-drug timing interaction, not a depletion. Plasma protein binding over 99%, mainly albumin. No absorption transporter is named in the sections retrieved.[1][3][4]
Hepatic and renal impairment, age
Cirrhosis: Cmax and AUC 50 to 60% higher; the drug is contraindicated in hepatic impairment including cirrhosis. Renal impairment: no apparent difference, no dose adjustment. Elderly: Cmax and AUC about 2 to 3 times those of younger adults.[1]
Other interactions
Erythromycin lowered zafirlukast levels about 40% (reduced bioavailability); aspirin raised them about 45%; fluconazole (moderate CYP2C9 inhibitor) raised them about 58%; itraconazole had no effect. Theophylline: rare reports of raised theophylline levels, mechanism unknown.[1]
Mineral, antacid and vitamin interactions
None listed. The label contains no statements about vitamins, minerals or supplements. Magnesium stearate and titanium dioxide appear only as inactive ingredients.[1] (label read through a summarizing fetch; section numbering did not match the usual PLR layout, so facts are cited by content)

What the research says is worth watching

General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.

  • Dosing timing / nutrient-to-drug

    Take apart from meals

    Food lowers mean zafirlukast bioavailability by about 40%. The label says at least 1 hour before or 2 hours after meals [1]. This is a drug-absorption interaction, not a depletion. No vitamin or mineral separation interval is given in the label. No supplement dose is recommended here.

  • Lab / safety (not nutrient)

    Liver tests

    The label warns of life-threatening hepatic failure and advises checking liver tests (ALT) and stopping the drug if liver dysfunction is suspected. It is contraindicated in hepatic impairment [1]. This is a drug toxicity, not a nutrient finding.

  • Drug interaction

    Warfarin and INR

    Zafirlukast raised S-warfarin AUC 63% and prothrombin time about 35%; the label advises close prothrombin time monitoring [1]. Not a vitamin K finding.

  • Research signal

    Folate-related drugs

    A 2026 laboratory study reports folate transporter inhibition by zafirlukast and other leukotriene receptor antagonists, with authors recommending monitoring when combined with antifolates such as methotrexate or pemetrexed [5]. Human data are absent. No routine folate test is supported by this review.

  • At-risk groups

    Elderly, hepatic impairment

    Older adults have about 2 to 3 times the exposure of younger adults, and cirrhosis raises Cmax and AUC by 50 to 60% [1]. Erythromycin lowers, and aspirin and fluconazole raise, zafirlukast levels [1].

  • Special populations

    Pregnancy, pediatrics, renal

    The label gives no renal adjustment [1]. It is indicated from age 5 [1]. Pregnancy and lactation nutrient considerations were not assessed from the sections retrieved. No nutrient-related population risk was found, so none is listed.

Overlap map, to prevent double counting

  • Oxidative stress

    Shares evidence with: Mitochondrial burden; ATP production

    Note: All three use the Bioengineered 2021 LO-2 hepatocyte study [7] (oxidative DNA damage, membrane potential and ATP in one experiment). One experiment, not three independent confirmations.

  • Mitochondrial burden

    Shares evidence with: Oxidative stress; ATP production

    Note: Shares [7]. The bronchial epithelial biogenesis study [6] supports only mitochondrial burden; the neutrophil and endothelial ROS records [9] support only oxidative stress.

  • ATP production

    Shares evidence with: Gut microbiome risk

    Note: Both use the S. agalactiae NDH-2 respiration result [8], read once as a human-ATP-irrelevant bacterial finding and once as an antibacterial finding. One source.

  • Folate

    Shares evidence with: None

    Note: Rests on the 2026 transporter study [5] alone. No shared source with any other entry.

  • Copper; Iron; Oxygen delivery/utilization

    Shares evidence with: Each other

    Note: All three are ungraded on the same null PubMed queries and the same absent label statements. Graded as separate entries per Hard Rule 7, but the underlying gap is shared.

  • Vitamin K; Vitamin D

    Shares evidence with: Folate (search only)

    Note: The compound vitamin query that surfaced the folate study [5] returned nothing for vitamin K or D. Shared search, no shared evidence.

All references used above
  1. Zafirlukast tablets, film coated, prescribing information (Aurobindo Pharma, DailyMed generic label). — Regulatory label (Tier A). Page header read "Updated December 1, 2023". Read through WebFetch, which returns a model summary, not raw text; no section 12.3 heading was found, so facts are cited by content. Source of food effect, CYP2C9 and CYP3A4, warfarin, hepatotoxicity, interactions, and the absence of any vitamin or mineral statement. A DailyMed search returned 8 generic zafirlukast labels and no Accolate-branded label.
  2. Wikipedia: Zafirlukast. — Tier D reference, used for ATC code R03DC01 and brand names only, and as a secondary statement of hepatotoxicity mechanism (unverified). Read through a summarizing fetch. The WHO ATC/DDD page was not opened.
  3. PubChem compound record, zafirlukast (pug_view, Drug and Medication Information). — Reference database (not Tier A for a depletion claim). Summarized fetch; only dosing-with-meals guidance found.
  4. Drugs.com: Zafirlukast food and lifestyle interactions. — Tier D consumer reference. Used only as a circulating-claim check. Summarized fetch.
  5. Luo J, Pan X, Bai M, Liu D, Ma S, Lin N, Wang Y. Leukotriene receptor antagonists inhibit SLC19A1 and SLC46A1-mediated transport of folic acid and antifolates. Chem Biol Interact 2026;439:112345. — In vitro transport assays and mouse pharmacokinetics (Tier B for zafirlukast). PMID 42716456; DOI 10.1016/j.cbi.2026.112345. Abstract read as a paraphrase through a summarizing fetch of a PubMed export. Bibliographic metadata and keywords confirmed from OpenAlex (abstract field null there) and Crossref (no abstract). Full text not opened (publisher page blocked by robots rules).Abstract-level, paraphrased; mouse doses, n and effect sizes not seen. Includes montelukast, pranlukast and MK571 alongside zafirlukast; only zafirlukast statements are used.
  6. Zafirlukast promotes mitochondrial respiration by stimulating mitochondrial biogenesis in human bronchial epithelial cells. J Mol Histol 2021. — In vitro (Tier B). PMID 33977464. Paraphrased abstract via summarizing fetch of a PubMed export.
  7. Zafirlukast ameliorates Docetaxel-induced activation of NLRP3 inflammasome, mediated by SIRT1 in hepatocytes. Bioengineered 2021. — In vitro, human LO-2 hepatocytes (Tier B). PMID 34787067. Paraphrased abstract via summarizing fetch.
  8. Type 2 NADH dehydrogenase is the only point of entry for electrons into the Streptococcus agalactiae respiratory chain and is a potential drug target. mBio 2018. — Drug screen plus mouse infection model of gene loss (Tier B for the zafirlukast result). PMID 29970468. Paraphrased abstract via summarizing fetch.
  9. PubMed listing, query "zafirlukast reactive oxygen species" (16 results reported, 10 shown). — Listing-level summaries only, abstracts not individually opened: PMID 24672130 (Curr Ther Res 2005, human neutrophils), 30594784 (Biomed Pharmacother 2019), 31745068 (Med Sci Monit 2019), 37580467 (Sci Rep 2023), 36122633 (Fish Shellfish Immunol 2022), 38092068 (Dev Comp Immunol 2024).
  10. Antineoplastic properties of zafirlukast against hepatocellular carcinoma via activation of mitochondrial mediated apoptosis. Regul Toxicol Pharmacol 2019. — In vitro (Tier B). PMID 31605713. Title and one excerpt line only, from a PubMed listing for "zafirlukast mitochondrial"; abstract not opened.
  11. Second generation of zafirlukast derivatives with improved activity against the oral pathogen Porphyromonas gingivalis. ACS Med Chem Lett 2020. — In vitro medicinal chemistry (Tier B, weak relevance). PMID 33062172. One-line summary from a PubMed listing for "zafirlukast dysbiosis"; abstract not opened.
  12. PubMed listing, query "zafirlukast warfarin" (9 records). — Listing-level summaries only. In vitro CYP2C9 inhibition in human liver microsomes: Xenobiotica 2004 (PMID 15370959, Ki about 5.86 uM) and Biopharm Drug Dispos 1999 (PMID 10870095, tolbutamide IC50 about 7.0 uM); pharmacokinetic review Clin Pharmacokinet 2002 (PMID 11888331). No record reported vitamin K data.
  13. PubMed listing, query "zafirlukast ATP" (9 records). — Listing-level summaries. Used to confirm that only PMID 34787067 and 29970468 report a zafirlukast effect on an ATP or respiration readout; other records concern ABC transporters or helicase docking.