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Total and free mycophenolic acid and its 7-O-glucuronide metabolite in Chinese adult renal transplant patients: pharmacokinetics and application of limited sampling strategies
- Source :
- European journal of clinical pharmacology. 63(1)
- Publication Year :
- 2006
-
Abstract
- This study aimed to investigate the pharmacokinetic characteristics of total and free mycophnolic acid (MPA) and its 7-O-glucuronide metabolite (MPAG) in Chinese renal transplant recipients. In addition, limited sampling strategies were developed to estimate the individual area under concentration curve (AUC) of total and free MPA. Total and free MPA and MPAG concentrations were determined by high performance liquid chromatography. Whole 12-h pharmacokinetic profiles were obtained on the 10th day after operation in 12 adult Chinese de novo renal transplant recipients administrated with mycophenolate mofetil (MMF, 750 mg bid), cyclosporine and corticosteroids. Limited sampling strategies with jackknife technique, a resampling method, and Bland-Altman analysis were employed to develop equations to estimate total and free MPA AUC. The pattern of total and free MPA and MPAG plasma concentration-time curves in the cohort of patients taking lower doses of MMF was consistent with previous reports of Caucasian patients taking MMF 1 g bid, except that dose-normalized exposure of total and free MPAG was much lower in the current study than in those of the Caucasians. The mean C max and AUC0–12h of total and free MPA were 9.4 ± 3.4 mg/L, 20.2 ± 6.5 mg·h/L and 0.4 ± 0.4 mg/L, 0.7 ± 0.5 mg·h/L, respectively, whereas mean C max and AUC0–12h of total and free MPAG were 97.3 ± 32.6 mg/L, 656.0 ± 148.0 mg·h/L and 29.9 ± 8.5 mg/L, 222.0 ± 58.1 mg·h/L respectively. The mean fractions of free MPA and MPAG were 3.5 ± 2.0 and 34.6 ± 8.0%, respectively. No determinant was identified to influence the pharmacokinetics of total and free MPA and MPAG or the free fraction of MPA and MPAG. The combinations of C 2h−C 4h and C 1h-C 2h-C 3h were the best to estimate free and total MPA AUC0–12h respectively, whereas the combination of C 2h-C 3h-C 4h and C 1h-C 2h-C 4h was the best to estimate both simultaneously. This is the first time that the pharmacokinetics profile of total and free MPA and its main metabolite MPAG has been examined in Chinese adult renal transplant patients. The limited sampling strategies proposed to estimate individual free and total MPA AUC could be useful in optimizing patient care.
- Subjects :
- Adult
Male
medicine.medical_specialty
China
Metabolite
Urology
Mycophenolate
High-performance liquid chromatography
Mycophenolic acid
chemistry.chemical_compound
Glucuronides
Pharmacokinetics
Asian People
medicine
Humans
Pharmacology (medical)
Prodrugs
Chromatography, High Pressure Liquid
Pharmacology
business.industry
General Medicine
Blood Proteins
Middle Aged
Mycophenolic Acid
Kidney Transplantation
Surgery
Transplantation
chemistry
Free fraction
Area Under Curve
Female
business
Glucuronide
Immunosuppressive Agents
medicine.drug
Protein Binding
Subjects
Details
- ISSN :
- 00316970
- Volume :
- 63
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- European journal of clinical pharmacology
- Accession number :
- edsair.doi.dedup.....6a703c8148689c4bc4ae3e9a93b6dfc0