Effects of Rifampin on the Pharmacokinetics of a Single Dose of Istradefylline in Healthy Subjects.
Abstract: Istradefylline, a selective adenosine A2A inhibitor, is under development for the treatment of Parkinson's disease. The effect of oral steady‐state rifampin 600 mg/day, a potent cytochrome P450 (CYP) 3A4 inducer, on the disposition of a single oral dose of istradefylline 40 mg was determin...
| Publicado en: | Journal of Clinical Pharmacology Vol. 58; no. 2; pp. 193 - 202 |
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| Autores principales: | , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Feb2018
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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=127241726&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 127241726 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: Feb2018 vid: 58 iid: 2 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 127241726 127241726 127241726 10.1002/jcph.1003 127241726 ppf: 193 ppct: 9 formats: tig: atl: Effects of Rifampin on the Pharmacokinetics of a Single Dose of Istradefylline in Healthy Subjects. aug: au: Mukai, Mayumi Uchimura, Tatsuo Zhang, Xiaoping Greene, Douglas Vergeire, Maria Cantillon, Marc affil: Kyowa Kirin Pharmaceutical Development, Inc., Princeton, NJ, USA sug: subj: Rifampin Pharmacodynamics Receptors, Cell Surface Pharmacokinetics Research Subjects Drug Interactions Cytochrome P-450 Enzyme System Drug Effects Crossover Design Human Confidence Intervals ab: Abstract: Istradefylline, a selective adenosine A2A inhibitor, is under development for the treatment of Parkinson's disease. The effect of oral steady‐state rifampin 600 mg/day, a potent cytochrome P450 (CYP) 3A4 inducer, on the disposition of a single oral dose of istradefylline 40 mg was determined in a crossover study in 20 healthy subjects by measuring plasma concentrations of istradefylline and its M1 and M8 metabolites and their derived pharmacokinetic parameters. Based on the geometric mean ratio of log‐transformed data, rifampin reduced istradefylline exposure: Cmax, 0.55 (90%CI, 0.49–0.62); AUClast, 0.21 (90%CI, 0.19–0.22); and AUCinf, 0.19 (90%CI, 0.18–0.20), indicating nonequivalence. These changes were primarily because of the effect of rifampin on the elimination parameters of istradefylline; mean CL/F was increased from 4.0 to 20.6 L/h, and mean t1/2 was reduced from 94.8 to 31.5 hours. The effect of rifampin coadministration on the disposition of the istradefylline M1 and M8 metabolites was inconsistent and variable. Furthermore, as exposure of the istradefylline M1 and M8 metabolites in plasma was generally <9% of total drug exposure, it would be expected to have a negligible impact on the pharmacodynamic effect of istradefylline. Caution should be exercised when istradefylline is administered concurrently with strong CYP3A4 inducers and dose adjustment considered. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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