RT Journal Article
SR Electronic
T1 Pharmacokinetic Differences Corroborate Observed Low Tacrolimus Dosage in Native American Renal Transplant Patients
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 2017
OP 2019
DO 10.1124/dmd.111.041350
VO 39
IS 11
A1 Anita Grover
A1 Lynda A. Frassetto
A1 Leslie Z. Benet
A1 Harini A. Chakkera
YR 2011
UL http://dmd.aspetjournals.org/content/39/11/2017.abstract
AB We have observed in clinical practice that Native Americans require lower dosages of tacrolimus to attain similar target blood trough levels compared to whites after renal transplant. Because there are no pharmacokinetic studies of tacrolimus in this ethnic group, we investigated whether this clinical observation could be corroborated by pharmacokinetic differences between Native Americans and other ethnic and racial groups. We recruited 24 adult Native American kidney transplant recipients on stable oral doses of tacrolimus for at least 1 month posttransplant. We conducted a 12-h steady-state pharmacokinetic profile for all of the patients and estimated pharmacokinetic parameters using NONMEM. The concentration-time data were fit to a linear two compartment model with first-order absorption and lag time using an empirical Bayesian approach. The mean estimate of oral clearance (CL/F) was 11.1 l/h. Compared with previously reported data in other ethnic and racial groups, the Native American cohort has approximately one third the clearance of other groups. Our pharmacokinetic study reveals the clinically observed low dose of tacrolimus in Native American renal transplant patients is associated with a decreased oral tacrolimus clearance. There is scant information available on the genetic or environmental characteristics unique to this ethnic group that affect pharmacokinetics compared to other, better-studied groups, and elucidation of these factors will provide information to further facilitate individualized drug treatment for tacrolimus and a wide range of other drugs with similar clearance processes.