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The kinetics of mycophenolic acid and its glucuronide metabolite in adult kidney transplant recipients
Author(s) -
Johnson Anthony G.,
Rigby Russell J.,
Taylor Paul J.,
Jones Christopher E.,
Allen Joan,
Franzen Kirsten,
Falk Michael C.,
Nicol David
Publication year - 1999
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(99)70012-3
Subject(s) - mycophenolic acid , transplantation , mycophenolate , creatinine , pharmacokinetics , kidney transplantation , area under the curve , therapeutic drug monitoring , pharmacology , medicine , chemistry , urology
Background Mycophenolic acid kinetics have been reported to vary after renal transplantation, and mycophenolic acid area under the concentration–time curve (AUC) is the best predictor of suppression of graft rejection. Methods To determine whether mycophenolic acid kinetics vary after renal transplantation and to examine the potential role of enterohepatic recirculation, we investigated the kinetics of mycophenolic acid and mycophenolic acid glucuronide on days 2, 5, and 28 after transplantation in 10 kidney transplant recipients (male/female ratio, 1.5; mean age, 41.7 ± 5.0 years) given 1 g mycophenolate mofetil twice a day. To facilitate therapeutic drug monitoring, we examined a limited sampling strategy for estimating 12‐hour mycophenolic acid [AUC(0–12)]. Results The mean ± SE AUC(0–12) for mycophenolic acid on day 28 was 38.5 ± 1.6 mg · h/L, with a secondary peak 4 to 8 hours after dosing that was attributable to enterohepatic recirculation. Marked variability was shown in the kinetic profile of mycophenolic acid among patients across the three sampling days. Mycophenolic acid AUC(0–12) was positively predicted by both serum creatinine ( P = .01) and serum albumin ( P = .03) but not by time after transplantation, body weight, or trough concentration. Limited sampling (at 0, 1, 3, and 6 hours) accounted for 84.1% of the variability in the mycophenolic acid AUC(0–12) data and predicted the AUC(0–12) closely ( r 2 = 0.954) when evaluated in 10 different kidney transplant recipients. Conclusions Mycophenolic acid AUC(0–12) is predicted by serum albumin and creatinine after kidney transplantation, and the AUC(0–12) may be determined during the early posttransplant period while the patient remains hospitalized with use of a limited sampling strategy to facilitate therapeutic drug monitoring. Clinical Pharmacology & Therapeutics (1999) 66 , 492–500; doi: