Cyclosporine pharmacokinetics and pharmacodynamics in African American and white subjects.

Abstract

Renal allograft survival is lower in African American patients compared with white patients. Interethnic differences in cyclosporine (INN, ciclosporin) pharmacokinetics in renal transplant recipients have been described but have not been well characterized. Pharmacodynamic responses to cyclosporine have not been compared among ethnic groups. Healthy men were studied after 5 days on a controlled diet. Cyclosporine concentrations were determined in whole blood drawn at intervals over 24 hours after administration of a microemulsion cyclosporine formulation (4 mg/kg; 9 African American subjects and 9 white subjects) and after a standard cyclosporine formulation (4 mg/kg; 10 African American subjects and 10 white subjects). Inhibition of phytohemagglutinin-P-stimulated interleukin-2 production in whole blood drawn 4 hours after cyclosporine was used as a pharmacodynamic measure to compare the effect of cyclosporine in African American and white subjects. The microemulsion cyclosporine formulation (area under the cyclosporine concentration-time curve, 7432 +/- 560 ng. h/mL in African American subjects and 7043 +/- 454 ng. h/mL in white subjects) was more bioavailable than the standard formulation (area under the cyclosporine concentration-time curve, 4828 +/- 319 ng. h/mL in African American subjects and 4538 +/- 301 ng. h/mL in white subjects); this resulted in an approximately 50% greater area under the cyclosporine concentration-time curve (P < .001 in both ethnic groups). There were no differences between African American subjects and white subjects in any pharmacokinetic measurement, with both the standard and the microemulsion cyclosporine formulations. Inhibition of phytohemagglutinin-P-stimulated interleukin-2 production 4 hours after the administration of cyclosporine was similar in African American subjects (70% +/- 5% inhibition) and white subjects (64% +/- 7% inhibition; P = .5). The pharmacokinetics and pharmacodynamics of cyclosporine were similar in a matched group of African American and white subjects studied under controlled conditions. Environmental factors may contribute more than genetic variability to the lower bioavailability of cyclosporine reported in African American renal transplant recipients.