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PhD Student, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
Clinical Assistant Professor, Faculty of Pharmaceutical Sciences, University of British Columbia; Clinical Coordinator and Clinical Pharmacy Specialist, Pharmaceutical Sciences Clinical Services Unit, Vancouver General Hospital, Vancouver
Associate Professor, Faculty of Medicine, University of British Columbia; Medical Director, Lung Transplant Program, British Columbia Transplant Society; Division of Respiratory Medicine, Vancouver Hospital & Health Sciences Centre; James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Vancouver
Professor, Faculty of Pharmaceutical Sciences, University of British Columbia
Professor and Director, Doctor of Pharmacy Program, Faculty of Pharmaceutical Sciences, University of British Columbia; Clinical Pharmacy Specialist, Pharmacy Department, Children's & Women's Health Centre of British Columbia, Vancouver
Reprints: Dr. Ensom, Department of Pharmacy (0B7), Children's & Women's Health Centre of British Columbia, 4500 Oak St., Vancouver, British Columbia, V6H 3N1, fax 604/875-3735, ensom{at}interchange.ubc.ca
BACKGROUND: Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil, an immunosuppressive agent commonly used in solid organ transplantation. MPA is metabolized to the inactive metabolite 7-O-mycophenolic acid glucuronide (MPAG) and the active metabolite acyl glucuronide (AcMPAG). Pharmacokinetic profiling of MPA by determining AUC is a tool for determining drug exposure. Many studies, conducted primarily in kidney and some heart and liver transplant recipients, have shown wide interpatient variability in MPA's pharmacokinetic parameters. There have been few studies in the lung transplant group and, even though the lung is not involved in drug elimination, these patients may have different MPA pharmacokinetic characteristics.
OBJECTIVE: To characterize the pharmacokinetic parameters and metabolic ratios of MPA in stable adult lung transplant recipients.
METHODS: In an open-label manner, lung transplant recipients were recruited. Blood samples were obtained at 0, 0.3, 0.6, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours postdose. Plasma was separated and acidified for drug concentration analysis (MPA, MPAG, AcMPAG) by an HPLC-ultraviolet detection method. Conventional pharmacokinetic parameters were determined via noncompartmental methods.
RESULTS: There was large interpatient variability in all pharmacokinetic parameters of MPA, MPAG, and AcMPAG. Similar variability was observed after stratifying patients into concomitant medication groups: cyclosporine and tacrolimus. There was a trend for the tacrolimus group to have a higher dose-normalized AUC, higher AUC, lower apparent clearance, and lower AUC ratio of AcMPAG/MPA compared with the cyclosporine group. In addition, the cyclosporine group had a lower minimum concentration and higher AUC ratio of MPAG/MPA than did the tacrolimus group (p < 0.05).
CONCLUSIONS: Because of the large interpatient variability in the pharmacokinetic parameters of MPA, MPAG, and AcMPAG, therapeutic drug monitoring of MPA and its metabolites in lung transplant recipients may be beneficial.
Key Words: lung transplant, mycophenolic acid, pharmacokinetics
Published Online, August 1, 2006. www.theannals.com, DOI 10.1345/aph.1H149
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