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 ��g��mL-1, lower limit of quantization was 0.10 ��g��mL-1.The main pharmacokinetic parameters on day 7 of MMF dispersible tablets were as follows:AUC0-12 h was (24.63��9.51) ��g��h��mL-1, ��max was (6.51��3.27) ��g��mL-1, tmax was (1.83��1.30) h, ��0 was (1.26��0.99) ��g��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, ��max and ��0 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.
STAATZ C E, TETT S E. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients[J]. Clin Pharmacokinet, 2007,46(1):13-58.
[2]
VAN GELDER T,HILBRANDS L B,VANRENTERGHEM Y,et al.A randomized double-blind,multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolatemofetil for the prevention of acute rejection after kidney transplantation[J].Transplantation,1999,68(2):261-266.
[3]
DE WINTER B C, MATHOT R A, VAN HEST R M, et al. Therapeutic drug monitoring of mycophenolic acid:does it improve patient outcome[J]. Expert Opin Drug Metab Toxicol, 2007,3(2):251-261.
[4]
KANG J, PU F F, LIU Y G, et al. Determination of mycophenolic acid in plasma by reversed phase high performance liquid chromatography with solidphase extraction [J]. Chin Pharm J(�й�ҩѧ��־), 2001,36(5):331-333.
[5]
LI P M, ZHANG X L, TANG K, et al. Determination of mycophenolic acid concentration in human plasma and its application to therapeutic drug monitoring in renal transplantation patient[J]. Chin Pharm J(�й�ҩѧ��־),2007, 42 (19):1490-1492.
[6]
DE WINTER B C, MATHOT R A, SOMBOGAARD F, et al. Nonlinear relationship between mycophenolatemofetil dose and mycophenolic acid exposure:implications for therapeutic drug monitoring[J]. Clin J Am Soc Nephrol, 2011, 6(3):656-663.
[7]
CIANCIO G,MILLER J,GONWA T A. Review of major clinical trials with mycophenolatemofetil in renal transplantation[J]. Transplantation,2005,80(2 suppl):191-200.
[8]
SHUM B, DUFFULL S B, TAYLOR P J, et al. Population pharmacokinetic analysis of mycophenolic acid in renal transplant recipients following oral administration of mycophenolate mofetil[J]. Br J Clin Pharmacol, 2003, 56(2):188-197.
[9]
ZHANG Q, TAO Y F, ZHU Y B, et al. Bioequivalence and pharmacokinetic comparison of two mycophenolate mofetil formulations in healthy Chinese male volunteers:an open-label, randomized-sequence, single-dose, two-way crossover study[J]. Clin Ther, 2010, 32(1):171-178.
[10]
VAN HEST R M, VAN GELDER T, BOUW R, et al. Time-dependent clearance of mycophenolic acid in renal transplant recipients[J]. Br J Clin Pharmacol, 2007, 63(6):741-752.
[11]
SAM W J, AKHLAGHI F, ROSENBAUM S E. Population pharmacokinetics of mycophenolic acid and its 2 glucuronidated metabolites in kidney transplant recipients[J]. J Clin Pharmacol, 2009,49 (2):185-195.
[12]
CATTANEO D,PERICO N,GASPARI F,et al. Glucocorticoids interfere with mycophenolate mofetil bioavailability in kidney transplantation[J]. Kidney Int,2002,62(3):1060-1067.
[13]
ROUSSEAU A, LAROCHE M L, VENISSE N, et al. Cost-effectiveness analysis of individualized mycophenolate mofetil dosing in kidney transplant patients in the APOMYGRE trial[J]. Transplantation, 2010, 89(10):1255-1262.
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