Population pharmacokinetics of cyclosporine in chinese cardiac transplant recipients.
OBJECTIVE
To characterize the population pharmacokinetics of cyclosporine in Chinese patients undergoing cardiac transplantation and to identify the demographic and clinical covariates affecting cyclosporine clearance.


METHODS
Population pharmacokinetic analysis using data from a retrospective chart review.


METHODS
Specialty hospital in Hong Kong for treatment of cardiac and pulmonary diseases.


METHODS
Thirty-eight Chinese adult patients (mean age 46 yrs) who had undergone routine cyclosporine therapeutic drug monitoring after cardiac transplantation between January 1, 1991, and December 31, 2003.


RESULTS
Data regarding dosing, demographics, clinical laboratory values, and concurrent drugs were collected retrospectively. Data were included if patients had blood cyclosporine concentrations determined for at least 12 weeks after transplantation; an average of 18 blood samples/patient were collected. Population modeling was performed using a one-compartment linear model with first-order absorption and elimination. Various demographic and clinical covariates were tested for their significant effects on the apparent oral clearance (Cl/F) of cyclosporine. The stability of the final population model was evaluated by using the bootstrap resampling method. Statistically significant associations were observed between Cl/F and each of the following covariates: body weight (BW), use of diltiazem (DIL), and hematocrit value (HCT). The final model was Cl/F=5.00*(1-DIL)+365/HCT+(0.144*BW). The interindividual variabilities of Cl/F and apparent volume of distribution were 14.5% and 40.2%, respectively. The mean parameter estimates obtained from bootstrap analyses were highly consistent with those obtained with the original data set.


CONCLUSIONS
The estimated Cl/F values of cyclosporine in our Chinese cardiac transplant recipients appeared to be similar to those reported for Caucasian cardiac transplant recipients. Thus, our data provide support that a cyclosporine dosage regimen similar to that in Caucasian patients may be needed in Chinese cardiac transplant recipients. However, further studies are required to determine the optimum cyclosporine dosage regimen in the Chinese population.
Yin
Ophelia Q P
OQ
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, and the Department of Pharmacy, Grantham Hospital, Aberdeen, Hong Kong. qpyin@cuhk.edu.hk
Lau
So-Kei
SK
Chow
Moses S S
MS
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D044466:Asian People / Q000706:statistics & numerical data*; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D016027:Heart Transplantation; D006723:Hong Kong; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D012189:Retrospective Studies
D007166:Immunosuppressive Agents; D016572:Cyclosporine