Gender-dependent racial difference in disposition of cyclosporine among healthy African American and white volunteers.
Pharmacokinetic studies of intravenous and oral cyclosporine (cyclosporin) were performed in 22 healthy African American (n = 11) and white (n = 11) volunteers. Blood cyclosporine concentrations were measured by high performance liquid chromatography. Concentration versus time data were analyzed by noncompartmental models, and statistical analyses were performed by ANOVA. The clearance of intravenous and oral cyclosporine was 4.3 +/- 0.9 mL/min/kg and 13.5 +/- 4.5 mL/min/kg, respectively, in African Americans and 3.7 +/- 0.5 mL/min/kg and 9.6 mL/min/kg, respectively, in the white volunteers (P = .0001). There was a significant race and gender interaction (P = .038). Bioavailability was lower in African Americans (32.8 +/- 6.6%) compared with white volunteers (39.3 +/- 7.1%; P = .049), with a significant race and gender interaction (P = .048). The dose-adjusted area under the curve (AUC) of intravenous and oral cyclosporine was 54.3 +/- 10.6 ng x hr/mL per milligram and 18.1 +/- 4.1 ng x hr/mL per milligram, respectively, in African Americans and 61.9 +/- 6.8 ng x hr/mL per milligram and 24.2 +/- 4.6 ng x hr/mL per milligram, respectively, in white volunteers (P = .023). These findings suggest that disposition of cyclosporine is dependent both on race and on gender.
Min
D I
DI
College of Pharmacy, Department of Internal Medicine, The University of Iowa, Iowa City 52242, USA. david-min@uiowa.edu
Lee
M
M
Ku
Y M
YM
Flanigan
M
M
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D044383:Black People; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D012737:Sex Factors; D044465:White People; D001741:Black or African American
D007166:Immunosuppressive Agents; D016572:Cyclosporine