LI Zhong-dong1��GUO Yan-ping1��SHI Xiao-jin1��YU Yun-qiu2��GENG Fang1��SHEN Min1��ZHONG Ming-kang1
1. Division of Clinical Pharmacy Research, Huashan Hospital,Fudan University,Shanghai 200040, China�� 2.School of Pharmacy, Fudan University , Shanghai 201203, China
Abstract��
OBJECTIVE To evaluate the steady-state pharmacokinetics and the bioequivalence of 3 oral compound levodopa preparations in 18 Chinese healthy male volunteers. METHODS Multiple oral doses of 3 compound levodopa preperations, i.e. test 1�� Sinemet CR tablet and entacapone tablet, test 2�� Madopar tablet and entacapone tablet, and reference�� Sinemet CR tablet, were given to 18 healthy volunteers in a randomized crossover study. The concentrations of levodopa were determined by HPLC-MS/MS method. RESULTS The main pharmacokinetic parameters of the 3 preparations were as follows�� AUC0-12(3 657.57��683.27), (2 365.87��597.81) and (3 017.48��612.99)ng��h��mL-1����max (809.56��128.40), ��742.50��152.81��and (746.83��148.53) ng��mL-1��tmax (2.53��0.50), ��1.42��0.70��and (2.19��0.71) h��MRT0-inf (6.57��2.15), ��6.04��1.91��and (6.75��2.80) h ��t1/2 (2.96��1.04), ��2.72��1.43��and (2.87��1.12) h��respectively. The relative bioavailability of test 1 and test 2 tablets to reference tablets were (128.77��47.69)% and��80.43��20.11��%��respectively. There were significant differences in the main pharmacokinetic parameters between the 3 preparations (P<0.05). CONCLUSION The RESULTS of statistical analysis demonstrated that the relative bioavailability of two test preparations were nonbioequivalent to the reference one, but their ��max were both bioequivalent to the reference tablets, and the tmax of test 1 had no difference with the reference (P>0.05), the tmax of the reference was greater than the one of test 2 (P<0.05) .
LI Zhong-dong,
GUO Yan-ping,
SHI Xiao-jin etc
.Study on the Steady-State Pharmacokinetics and Bioequivalence of Three Oral Compound Levodopa Preperations in Healthy Male Volunteers[J] Chinese Pharmaceutical Journal, 2011,V46(24): 1923-1928
��
[1]
PAIJA O�� LAINE K�� KULTALAHTI E R��et al. Entacapone increases levodopa exposure and reduces plasma levodopa variability when used with sinemet CR[J]. Clin Neuropharmcol��2005��28(3)��115-119.[2] AHTILA S, KAAKKOLA S, GORDIN A, et al. Effect of entacapone, a COMT inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of controlled-release levodopa/carbidopa in volunteers[J]. Clin Neuropharmacol�� 1995,18��1����46-57.[3] PICCINI P, BROOKS D J, KORPELA K, et al. The catechol-O-methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson��s disease[J]. J Neurol Neurosurg Psychiatry�� 2000,68��5����589-594.[4] STOCCHI F, BARBATO L, NORDERA G, et al. Entacapone improves the pharmacokinetic and therapeutic response of controlled release levodopa/carbidopa in Parkinson's patients[J]. J Neural Transm, 2004,111��2����173-180.[5] GORDIN A, KAAKKOLA S, TER�ZV�ZINEN H. Position of COMT inhibition in the treatment of Parkinson's disease[J]. Adv Neurol�� 2003,91��237-250.[6] KAAKKOLA S. Clinical pharmacology, therapeutics and potential of COMT inhibitors in Parkinson's disease[J]. Drugs�� 2000,59��6����1233-1250.[7] NUTT J G, WOODWARD W R, BEEKNER R M, et al. Effects of an inhibitor of catechol-O- methyltransferase (COMT) on the pharmacokinetics and pharmacodynamics of levodopa[J]. Neurology�� 1994,44��5����913-919[8] KAAKKOLA S, TER�ZV�ZINEN H, AHTILA S, et al. Entacapone in combination with standard or controlled release levodopa/carbidopa�� a clinical and pharmacokinetic study in patients with Parkinson's disease[J]. Eur J Neurol�� 1994,44(1)��77-80.[9] MUZZI C, BERTOCCI E, TERZUOLI L, et al. Simultaneous determination of serum concentrations of levodopa, dopamine, 3-O-methyldopa and a-methyldopa by HPLC[J]. Biomed Pharmacother, 2008,62(4)��253-258.[10] YEH K C, AUGUST T F, BUSH D F, et al. Pharmacokinetics and bioavailability of Sinemet CR�� a summary of human studies[J]. Neurology�� 1989,39(11 suppl 2)��25-38.
2011, Vol. 46 
