Intersubject variation in the pharmacokinetics of haloperidol and reduced haloperidol.
Single oral doses (5 mg) of haloperidol were administered to 36 healthy men (26 black, 10 white) of whom 28 (22 black, 6 white) completed the study. Plasma samples harvested over 96 hours were analyzed for haloperidol and reduced haloperidol by means of a new high performance liquid chromatographic method. Reduced haloperidol was detectable in the plasma of only six of the 28 subjects (five blacks, one white). In these individuals reduced haloperidol plasma concentrations were generally much lower than those of the parent drug. This finding in the present single-dose study is in contrast to literature reports that have described levels of reduced haloperidol higher than those of the parent drug in some patients chronically mediated with haloperidol. There was wide intersubject variation in area under the plasma concentration versus time curve and apparent oral clearance values for haloperidol. The distributions of these pharmacokinetic parameters about their respective means were each leptokurtotic and skewed toward higher values. In each case the geometric mean gave a better estimate of central tendency than the arithmetic mean. Wide intersubject variation prevented the detection of significant differences in these pharmacokinetic parameters between black and white subjects or between smokers and nonsmokers.
Midha
K K
KK
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
Chakraborty
B S
BS
Ganes
D A
DA
Hawes
E M
EM
Hubbard
J W
JW
Keegan
D L
DL
Korchinski
E D
ED
McKay
G
G
D000293:Adolescent; D000328:Adult; D044383:Black People; D002851:Chromatography, High Pressure Liquid; D006220:Haloperidol / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007206:Individuality; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D012907:Smoking / Q000378:metabolism; D044465:White People
D006220:Haloperidol