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

Study Overview
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Brief Summary
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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

Detailed Description
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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. --------------------------------------------------------------------------------

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

Conditions
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Cytochrome P450 CYP3A5 Enzyme Polymorphism, Healthy Subjects, Pharmacokinetics of Maraviroc

Intervention / Treatment
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* Drug: Maraviroc


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maraviroc<br>single oral administration of 300 mg maraviroc | Drug: Maraviroc<br> <br> * Other names: Selzentry;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve |  | 0-32 hour post dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance |  | 0-32 hr post dose administration | 
| Plasma peak concentration |  | 0-32 hr post dose administration | 
| Plasma half-life |  | 0-32 hr post dose administration | 
| Urinary metabolic ratio |  | 0-32 hr post dose administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CYP3A5, maraviroc, polymorphism