RESUMO
OBJECTIVE: To investigate the pharmacokinetic characteristics of enteric-coated sodium mycophenolate(EC-MPS) or mycophenolate mofetil (MMF) dispersible tablets after multiple oral doses in early renal transplant patients, providing references for the rational use of the study drugs in clinical practice. METHODS: Thirty-eight first-time renal transplant patients were selected and randomly divided into EC-MPS group (n=18) or MMF dispersible tablets group (n=19). The patients received EC-MPS (540 mg, q12h) or MMF dispersible tablets (750 mg, q12h), combined with tacrolimus and methylprednisolone to prevent acute rejection, respectively. Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after oral administration on the postoperative day 5. Enzyme multiplied immunoassay technique (EMIT) was employed to determine the plasma concentration of MPA. The main pharmacokinetic parameters of the two durgs were assessed. RESULTS: Pharmacokinetic parameters on the postoperative day 5 of EC-MPS and MMF dispersible tablet were as follows: AUC0-12 h were(43.62±16.20) and(42.02±14.40)mg•h•L-1(P>0.05);ρmax were (17.85±11.32) and (13.96±5.11) mg•L-1(P>0.05);tmax were (2.72±1.74) and(1.32±0.42)h(P0.05); ρ12were(1.84±2.09) and (1.81±1.76) mg•L-1(P>0.05); CL were (14.12±5.30) and (19.66±5.99) L•h-1(P<0.05). Most of the patients revealed a second small peak in the 4-12 h after taking MPA in the two study groups. CONCLUSION: There are large individual differences of pharmacokinetic between EC-MPS and MMF dispersible tablets in early renal transplant patients. It is necessary to carry out therapeutic drug monitoring of MPA to guide the adjustment of drug dosage.
RESUMO
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.