Comparison of pharmacokinetic parameters of mycophenolic acid in two groups of Iranian kidney transplant patients

Abstract

Aim: Mycophenolate mofetil is widely used in organ transplantation to prevent acute rejection. Following oral administration, it is rapidly converted to mycophenolic acid (MPA). Effectiveness and the incidence of rejection is influenced by area under the concentration–time curve (AUC). Effect of time after transplantations on pharmacokinetic (PK) parameters is considered. Method: PK parameters of MPA was characterized in two different groups of Iranian kidney transplant patients. MPA plasma concentrations following oral administration of 1 g mycophenolate mofetil in a multiple dosage regimen were measured in 21 (group 1) and 31 (group 2) individuals. Group 1 for more than 3 months and group 2 had been transplanted for 9–10 days. Blood samples were taken before and at different time points following dose administration (0–12 h). Peak plasma concentration (Cmax), time to reach Cmax (Tmax), and AUC were calculated for each patient. Results: The first plasma peak was reached in the range of 0.6–2 and 0.3–2 h following dose intake in group 1 and group 2, respectively. In group 1, AUC, Cmax and time to reach Cmax were 47.6 ± 18.4 μg.h/ml, 17.9 ± 9.2 μg/ml and 1.0 ± 0.6 h respectively. In the second group, these values were 26.6 ± 19.0 μg.h/ml, 9.3 ± 6.1 μg/ml and 0.7 ± 0.6 h, respectively. Elimination rate constants were calculated for all the patients. In most of the patients, the three terminal points made the reliable results. Conclusion: The differences between PK parameters in these groups may be related to the length of time after transplantation and this must be considered in dose adjustment, probably decreasing the dose after few months to half and these may be performed in a proper clinical trial design.