Protein binding of rifapentine and its 25-desacetyl metabolite in patients with pulmonary tuberculosis.
Rifapentine is highly protein bound in blood, but the free, unbound drug is the microbiologically active fraction. In this exploratory study, we characterized the free plasma fraction of rifapentine in 41 patients with tuberculosis. We found a lower total rifapentine concentration but significantly higher free rifapentine levels in African patients of black race compared to non-Africans. These data support larger pharmacokinetic/pharmacodynamic studies to confirm these findings and assess free rifapentine in relation to microbiological and clinical outcomes.
College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Eric F
EF
Egelund
Departments of Medicine, University of Texas Health Science Center San Antonio and South Texas Veterans Health Care System, San Antonio, Texas, USA weiner@uthscsa.edu.
Marc
M
Weiner
Clinical Pharmacology Modeling and Simulation, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
Rajendra P
RP
Singh
Department of Pathology, University of Texas Health Science Center, San Antonio, Texas, USA.
Thomas J
TJ
Prihoda
Departments of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio, Texas, USA.
Jonathon A L
JA
Gelfond
College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Hartmut
H
Derendorf
Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
William R
WR
Mac Kenzie
College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Charles A
CA
Peloquin
D000328:Adult; D000904:Antibiotics, Antitubercular / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D001711:Biotransformation; D044383:Black People; D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology; D011485:Protein Binding; D012293:Rifampin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000188:drug therapy / Q000208:ethnology / Q000382:microbiology; D044465:White People
D000904:Antibiotics, Antitubercular; D001798:Blood Proteins; C032006:25-desacetylrifapentine; D012293:Rifampin; C018421:rifapentine