The effects of ketoconazole and rifampin on the single-dose pharmacokinetics of crizotinib in healthy subjects.
Purpose: To investigate the potential effects of strong CYP3A inhibitor ketoconazole and strong CYP3A inducer rifampin on the pharmacokinetics of crizotinib in human. Methods: Two separate open-label, 2-period, 2-treatment, 1-sequence, crossover, single-dose studies were conducted in healthy subject...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 71; no. 12; pp. 1441 - 1450 |
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| Autores principales: | , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Dec2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=110901326&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 110901326 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Dec2015 vid: 71 iid: 12 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 110901326 110901326 110901326 10.1007/s00228-015-1945-5 NLM26381275 110901326 ppf: 1441 ppct: 9 formats: fmt: @attributes: type: P tig: atl: The effects of ketoconazole and rifampin on the single-dose pharmacokinetics of crizotinib in healthy subjects. aug: au: Xu, Huiping O'Gorman, Melissa Tan, Weiwei Brega, Nicoletta Bello, Akintunde affil: Clinical Pharmacology, Oncology Business Unit, Pfizer Inc., 10646 Science Center Drive La Jolla 92121 USA sug: subj: Cytochrome P-450 Enzyme System Ketoconazole Rifampin Antineoplastic Agents Pharmacokinetics Drug Interactions Human Male Female Crossover Design Ketoconazole Administration and Dosage Rifampin Administration and Dosage Male Female ab: Purpose: To investigate the potential effects of strong CYP3A inhibitor ketoconazole and strong CYP3A inducer rifampin on the pharmacokinetics of crizotinib in human. Methods: Two separate open-label, 2-period, 2-treatment, 1-sequence, crossover, single-dose studies were conducted in healthy subjects with and without ketoconazole or rifampin. Series of plasma samples were collected after each crizotinib dose to determine concentration of crizotinib and its metabolite PF-06260182. Relevant pharmacokinetic (PK) parameters for crizotinib and PF096269182 were estimated by standard non-compartmental analysis (NCA) method. Results: Co-administration of a single 150-mg oral dose of crizotinib with the strong CYP3A inhibitor ketoconazole resulted in an area under the plasma-concentration curve extrapolated to infinity (AUC) 3.2-fold that for crizotinib alone. Co-administration of a single 250-mg crizotinib dose with the strong CYP3A inducer rifampin caused an 82 % decrease in crizotinib AUC. Respective increases and decreases in systemic exposure to the crizotinib metabolite PF-06260182 following co-administration of ketoconazole and rifampin were greater than those seen for crizotinib. Conclusions: These findings suggest that CYP3A plays an important role in the metabolism of both crizotinib and PF-06260182, with the extent of this role being greater for PF-06260182. There were no serious adverse events or deaths and no dose reductions or temporary or permanent discontinuations due to drug-related adverse events in either study. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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