Haloperidol의 약물속도론적 연구 (III) -정신분열증 환자에 있어서 Haloperidol의 일회 주사 및 경구투여시의 Pharmacokinetics

The pharmacokinetics of haloperidol were determined after single oral and intravenous doses in 13 male schizophrenic patients. Plasma concentrations of haloperidol(HP) and reduced haloperidol(RH) were measured by high performance liquid chromatography. Plasma concentration data obtained were analyzed by obth model dependent (one-or two exponential decay models using nonlinear regression) and model independent (AUC and first moment curve) approaches. The two methods were found to be in close results. After intravenous injections of HP in 8 patients (10 mg/man), the mean central and peripheral volume of distributions were $2.85\;{\pm}\;1.70$ and $8.09\;{\pm}\;2.10\;l/kg$, respectively, and mean steady state volume of distribution was $11.87\;{\pm}\;3.21\;l/kg$. Mean clearance, MRT and elimination half life were $12.39\;{\pm}\;3.25\;ml/min/kg$, $925.10\;{\pm}\;166.79\;min$ and $676.35\;{\pm}\;126.45\;min$, respectively. After oral administrations of HP in 5 patients, mean peak time and peak concentration were $217.63\;{\pm}\;61.60\;min$ and $9.77\;{\pm}\;2.92\;ng/ml$, respectively. Mean MRT and elimination half life were $1112.23\;{\pm}\;131.73\;min$ and $724.02\;{\pm}\;120.03\;min$, respectively, and these parameters were not significantly different from those of intravenous injection of HP. Absolute bioavailability of HP oral product was found to be about 44%. The profiles of plasma RH concentration-time curves after oral or intravenous doses of HP were similar. Also it was found that the elimination rate of RH was solwer than that of HP by comparing the slopes of plasma concentration-time curves of HP and RH.