title: Mycophenolic acid in diabetic renal transplant recipients: pharmacokinetics and application of a limited sampling strategy.
abstract: Limited sampling strategies may be useful in optimizing therapeutic drug monitoring of mycophenolic acid (MPA). Their use, however, may be limited by several patient factors, including comorbidity. In this study the pharmacokinetics of MPA in diabetic and nondiabetic renal transplant recipients were compared, and it was evaluated whether a limited sampling strategy developed and validated for nondiabetic patients can also be used in diabetic patients. The pharmacokinetics of MPA were analyzed on days 7 and 11 after transplantation in 136 renal transplant patients, among whom 7 patients had diabetes. All patients received cyclosporine and corticosteroids as maintenance immunosuppressive therapy. A limited sampling strategy [AUC (mg x h/L) = 7.182 + 4.607 C0 + 0.998 C0.67 + 2.149 C2] was developed and validated for nondiabetic patients and was subsequently tested for its usefulness in diabetic patients. Diabetic renal transplant patients did not have significantly different dose-normalized MPA area under concentration-time curve (AUC), MPA clearance, or MPA maximum concentration (Cmax). However, in diabetic patients Tmax (time of Cmax, 1.59 hours) was higher than for nondiabetic patients (0.67 hours) on day 11 (P = 0.04). The developed and validated limited sampling strategy performed acceptably, estimating MPA AUC in nondiabetic patients with a mean bias of 0.2 mg x h/L (95% confidence interval from -1.3 to 1.6 mg x h/L). Applying the limited sampling strategy in diabetic patients revealed a mean bias of -1.5 (-5.7, 2.7 mg x h/L). In conclusion, although diabetic renal transplant patients exhibit increased Tmax, this does not affect the accuracy of the limited sampling strategy.
authors.affiliation: Department of Hospital Pharmacy, Clinical Pharmacology Unit, Erasmus University Medical Center, Rotterdam, The Netherlands. r.vanhest@erasmusmc.nl
authors.forename: Reinier M
authors.initials: RM
authors.lastname: van Hest
authors.forename: Ron A A
authors.initials: RA
authors.lastname: Mathôt
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Vulto
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Meur
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016001:Confidence Intervals; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy; D016903:Drug Monitoring / Q000379:methods* / Q000706:statistics & numerical data; D005260:Female; D006084:Graft Rejection / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D016030:Kidney Transplantation; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012189:Retrospective Studies; D012494:Sampling Studies; D018709:Statistics, Nonparametric
chemical_list: D009173:Mycophenolic Acid