The effect of Madopar on the pharmacokinetics of ropinirole in healthy Chinese volunteers.
Ropinirole is a nonergoline dopamine D(2)-receptor agonist and has been proven to be effective in both monotherapy and combination therapy for idiopathic Parkinson's disease. The purpose of the present study was to examine the effect of Madopar on the pharmacokinetics of ropinirole in healthy Chinese volunteers by using liquid chromatography tandem mass spectrometry (HPLC/MS/MS). A single dose of 1mg ropinirole was given orally after administration of the placebo or Madopar (containing 200 mg levodopa and 50 mg benserazide) to six healthy males and six healthy females in a cross-over randomized study with a minimum washout period of 8 days. Pharmacokinetic parameters were calculated for both treatments. Coadministration of ropinirole and Madopar did not result in a notable change in rate or extent of availability of ropinirole, as shown by the ratios (90% confidence intervals) of 1.045 (0.900, 1.222) for C(max) (maximum plasma concentration) and 1.167 (1.086, 1.262) for AUC(0-inf) (the area under the concentration-time curve). Likewise, no significant difference in any of the other pharmacokinetic parameters [T(max) (the time needed to reach the C(max)), MRT (mean residence time), volume of distribution (V/F), and clearance (CL/F)] was observed between the treatment groups. No clinically relevant adverse effects were detected under either conditions and there are no pharmacokinetic grounds for adjusting the dose of ropinirole when given in combination with Madopar in Chinese patients.
Wen
Ai-Dong
AD
Department of Pharmacy, Xi'jing Hospital, Fourth Military Medical University, Xi'an 710032, PR China. adwen@fmmu.edu.cn
Jia
Yan-Yan
YY
Luo
Xiao-Xing
XX
Bi
Lin-Lin
LL
Chen
Xiao-Yan
XY
Zhong
Da-Fang
DF
D000328:Adult; D000978:Antiparkinson Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D044466:Asian People; D001545:Benserazide / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000097:blood / Q000493:pharmacokinetics*; D007980:Levodopa / Q000494:pharmacology*; D016014:Linear Models; D008297:Male; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods
D000978:Antiparkinson Agents; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007211:Indoles; C005177:benserazide, levodopa drug combination; C046649:ropinirole; D007980:Levodopa; D001545:Benserazide