Abstract:
:The disposition of simeprevir (SMV) in humans is characterised by cytochrome P450 3A4 metabolism and hepatic uptake by organic anion transporting polypeptide 1B1/3 (OATP1B1/3). This study was designed to investigate SMV plasma and liver exposure upon oral administration in subjects infected with hepatitis C virus (HCV), in subjects of Japanese or Chinese origin, subjects with organ impairment and subjects with OATP genetic polymorphisms, using physiologically based pharmacokinetic modelling. Simulations showed that compared with healthy Caucasian subjects, SMV plasma exposure was 2.4-, 1.7-, 2.2- and 2.0-fold higher, respectively, in HCV-infected Caucasian subjects, in healthy Japanese, healthy Chinese and subjects with severe renal impairment. Further simulations showed that compared with HCV-infected Caucasian subjects, SMV plasma exposure was 1.6-fold higher in HCV-infected Japanese subjects. In subjects with OATP1B1 genetic polymorphisms, no noteworthy changes in SMV pharmacokinetics were observed. Simulations suggested that liver concentrations in Caucasians with HCV are 18 times higher than plasma concentrations.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Snoeys J,Beumont M,Monshouwer M,Ouwerkerk-Mahadevan Sdoi
10.1007/s40262-016-0476-2subject
Has Abstractpub_date
2017-07-01 00:00:00pages
781-792issue
7eissn
0312-5963issn
1179-1926pii
10.1007/s40262-016-0476-2journal_volume
56pub_type
杂志文章abstract::Pharmacokinetic parameters of third generation cephalosporins vary widely, requiring different dosage regimens and adjustment methods for each agent. Although their antibacterial spectrum favours their usage in infections caused by aerobic Gram-negative organisms, due to their limited post-antibiotic effect against th...
journal_title:Clinical pharmacokinetics
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