Genetic polymorphism of catechol O-methyltransferase and pharmacokinetics of levodopa in healthy Chinese subjects.
We studied the distribution of catechol O-methyltransferase (COMT) genotypes in the Chinese Fujian Han population and explored the potential effect of COMT genetic polymorphism on the pharmacokinetics of levodopa. Polymerase chain reaction (PCR) was employed in the COMT genotype analysis of 166 volunteers. After a single oral dose of levodopa/benserazide, the plasma concentration of levodopa was determined by high-performance liquid chromatography (HPLC) with electrochemical detection (ECD). In the 166 subjects, the frequencies of G/G, G/A and A/A COMT genotypes were 58.4%, 36.7% and 4.9%, respectively. The frequency of the homozygous A/A genotype was much lower than in caucasians and Southwest Asians. COMT activity of erythrocytes in the G/A genotype group was significantly lower than in the G/G genotype group but significantly higher than in the A/A genotype group. There was no significant difference in pharmacokinetic parameters, including t(1/2alpha), t(1/2beta), AUC(0-infinity), CL/F, C(max), t(max) and V/F. The frequency of COMT genotypes in the Chinese Fujian Han population, which is related to COMT enzyme activity, is significantly different from that in caucasians and Southwest Asians. The pharmacokinetic characteristics of levodopa in healthy Chinese subjects may not be dependent on their COMT genotype status. From the 166 volunteers, 5 G/G, 5 G/A and 4 A/A genotype male subjects were recruited for the study of levodopa pharmacokinetics.
Lin
C-H
CH
Department of Pharmacology, Fujian Medical University; Department of Pharmacy, the First Affiliated Hospital, Fuzhou, Fujian, China.
Wang
C-L
CL
Huang
P-F
PF
Liu
Y-W
YW
Ke
M
M
Xu
Y
Y
Yu
C-X
CX
D000328:Adult; D000978:Antiparkinson Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics; D001545:Benserazide / Q000008:administration & dosage; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002681:China; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D006207:Half-Life; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics*; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics; D055815:Young Adult
D000978:Antiparkinson Agents; D004338:Drug Combinations; D007980:Levodopa; D001545:Benserazide; D002394:Catechol O-Methyltransferase