Characterization of the Effect of Upadacitinib on the Pharmacokinetics of Bupropion, a Sensitive Cytochrome P450 2B6 Probe Substrate.

Autor: Mohamed MF; AbbVie Inc., North Chicago, Illinois, USA., Minocha M; AbbVie Inc., North Chicago, Illinois, USA., Trueman S; AbbVie Inc., North Chicago, Illinois, USA., Feng T; AbbVie Inc., North Chicago, Illinois, USA., Enejosa J; AbbVie Inc., North Chicago, Illinois, USA., Fisniku O; AbbVie Inc., North Chicago, Illinois, USA., Othman AA; AbbVie Inc., North Chicago, Illinois, USA.
Jazyk: angličtina
Zdroj: Clinical pharmacology in drug development [Clin Pharmacol Drug Dev] 2021 Mar; Vol. 10 (3), pp. 299-306. Date of Electronic Publication: 2020 Jul 09.
DOI: 10.1002/cpdd.844
Abstrakt: This phase 1 study characterized the effect of multiple doses of upadacitinib, an oral Janus kinase 1 selective inhibitor, on the pharmacokinetics of the cytochrome P450 (CYP) 2B6 substrate bupropion. Healthy subjects (n = 22) received a single oral dose of bupropion 150 mg alone (study period 1) and on day 12 of a 16-day regimen of upadacitinib 30 mg once daily (study period 2). Serial blood samples for measurement of bupropion and hydroxybupropion plasma concentrations were collected in each study period. The central values (90% confidence intervals) for the ratios of change were 0.87 (0.79-0.96) for bupropion maximum plasma concentration (C max ), 0.92 (0.87-0.98) for bupropion area under the plasma-concentration time curve from time 0 to infinity (AUC inf ), 0.78 (0.72-0.85) for hydroxybupropion C max , and 0.72 (0.67-0.78) for hydroxybupropion AUC inf when administered with, relative to when administered without, upadacitinib. After multiple-dose administration of upadacitinib 30 mg once daily, upadacitinib mean ± SD AUC 0-24 was 641 ± 177 ng·h/mL, and C max was 83.3 ± 30.7 ng/mL. These results confirm that upadacitinib has no relevant effect on pharmacokinetics of substrates metabolized by CYP2B6.
(© 2020 AbbVie Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)
Databáze: MEDLINE
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