Polymorphic Effects of Cytochrome P450 3A5 on Pharmacokinetics of Maraviroc and Its Metabolites

Johns Hopkins University

Status and phase

Completed

Phase 1

Conditions

Healthy Subjects

Pharmacokinetics of Maraviroc

Cytochrome P450 CYP3A5 Enzyme Polymorphism

Treatments

Drug: Maraviroc

Study type

Interventional

Funder types

Other

Identifiers

NCT01980329

NA_00078492

Details and patient eligibility

About

The purpose of this study is to evaluate the influence of genetic polymorphism of cytochrome P450 3A5 on pharmacokinetics of maraviroc and its oxidative metabolites

Full description

This study aims to evaluate the effects of CYP3A5 genotype on pharmacokinetics of maraviroc and its oxidative metabolites. A single oral dose of 300 mg maraviroc will be given to 24 eligible healthy individuals who will be screened and determined to have specific CYP3A5 genotype - 8 homozygous wild type (2 CYP3A5*1 alleles), 8 heterozygous (1 CYP3A5*1 allele and 1 mutant allele), and 8 without wild type genotype (2 mutant alleles). Blood samples will be drawn and urine samples will be collected immediately before and during a 32-hr period following the dose. The concentrations of maraviroc and its oxidative metabolites from the blood and urine samples will be measured and the pharmacokinetics of maraviroc and its metabolites will be compared among the three groups with different CYP3A5 polymorphic status.

Enrollment

24 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy with no acute medical illness
Willing to provide written informed consent
Age 18-65 years
Negative serum pregnancy test (females only) at screening and a negative urine pregnancy test (females only) on day of dosing
HIV seronegative at screening, as determined by any licensed ELISA
At screening, no evidence of hepatic or renal impairment (LFT's < 1.5 Upper Limit of Normal (ULN), creatinine clearance > than 60 ml/min, total bilirubin below ULN, AST and ALT below 1.5 ULN)
8 subjects with homozygous CYP3A5 allele *1 (wild type)
8 subjects with 1 CYP3A5*1 allele and 1 mutant allele
8 subjects with CYP3A5 allele other than *1

Exclusion criteria

Concomitant medication (prescription or over-the-counter) or herbal supplements for which there is a known risk of pharmacokinetic or pharmacodynamic drug interactions, including those that inhibit CYP3A4 as listed on the P450 Drug Interaction Table (http://medicine.iupui.edu/clinpharm/ddis/table.aspx)
History of postural hypotension or cardiovascular disease
Active medical or psychological condition that, in the opinion of the investigator, might put the volunteer at undue risk or interfere with the participation of the study