Pharmacokinetics Study of Mycophenolate Mofetil Dispersible Tablets in Early Renal Transplant Patients / 中国药学杂志

ABSTRACT

OBJECTIVE: To develop an UPLC method for the determination of mycophenolic acid(MPA) for studying the pharmacokinetics of mycophenolate mofetil(MMF) dispersible tablets after multiple oral doses in early kidney transplant recipients for the rational use in the clinical practice. METHODS: A total of 15 Chinese postoperative renal transplant recipients were given a multiple-dose of MMF (750 mg, q12 h) for 6 d. Their blood specimens (2 mL) were collected at 0 and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after drug oral administration on day 7. The concentrations of MPA in plasma were determined using UPLC-UV. The main pharmacokinetic parameters were assessed. RESULTS: Determination of MPA had good linearity in the concentration range of 0.1-40 μg·mL-1, lower limit of quantization was 0.10 μg·mL-1.The main pharmacokinetic parameters on day 7 of MMF dispersible tablets were as follows AUC0-12 h was (24.63±9.51) μg·h·mL-1, ρmax was (6.51±3.27) μg·mL-1, tmax was (1.83±1.30) h, ρ0 was (1.26±0.99) μg·mL-1, CL was (34.66±12.45) L·h-1. Most of the patients revealed a second small peak in the 4-12 h. CONCLUSION: This established method is simple, rapid and suitable for determination of MPA in human plasma.Interindividual variability in AUC0-12 h, ρmax and ρ0 values was considerable in the early renal transplant patients. The MPA exposures under the fixed dose of MMF are low. It is necessary to monitor the MPA-AUC0-12 h to guide the adjustment of drug dosage.