15명의 정상 성인 남자에 대한 근육주사 및 경구투여후 Haloperidol의 약력학적 연구

Pharmacokinetics of Haloperidol After Intramuscular and Oral Administration in 15 Healthy Men

Pharmacokinetics of haloperidol were studied after intramuscular and oral administration in 15 healthy male volunteers. 10 mg of haloperidol were administered intramusculary to 9 subjects and the remainders received the same dose of haloperidol orally. In nine subjects, venous blood was sampled at 45，90，180，360，720，1440 min. after intramuscular dosing and in six subjects it was done at 90，180，360，720，1080，1440 min. after oral dosing. Serum haloperidol levels were determinded by high-performance liquid chromatography with ultraviolet detection. The detection limit of that method was 2ng/ml of haloperidol and the coefficient of variation was 5.4% at lOng/ml and it was 10.4% at 20ng/ml of heloperidol. In all subjects, data were analyzed by modelindependant approaches. Elimination half-life was determined in a model-independant manner by linear regression of the postdistribution. The linear trapezoidal rule was used to calculate area under the curve (AUC). In nine intramuscular subjects, mean elimination half-life was 19.8 士 8.4 hr and it was 19.8 ± 8.4 hr in six oral subjects. Our results do not demonstrate any differences between the two. Relative bioavailability(F) of oral haloperidol against intramuscular dosing was 47.2%. Because intravenous data were not available in our study, we used Ejm and F jq to calculate the value for clearance and volume of distribution. The mean steady-state volume of distribution/Fjyj was 6.8 ± 1.7L/kg and the mean clearance/F was 5.1 土 1.5 ml/kg/min. The mean steady-state volume of distribution/Fpq was 14.3 ± 3.6 L/kg and mean c le a r a n c e /Fw a s 5.1 ± 1.5 ml/kg/min.