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213 91 91 4 4 Y. F. Cheng Prof. Dr. L. K. Paalzow U. Bondesson B. Ekblom K. Eriksson S. O. Eriksson A. Lindberg L. Lindström Department of Biopharmaceutics and Pharmacokinetics Uppsala University S-751 23 Uppsala Sweden Uller↼er Hospital S-750 17 Uppsala Sweden Hospital Pharmacy Uller↼er Hospital S-750 17 Uppsala Sweden Department of Biopharmaceutics and Pharmacokinetics Box 580 S-751 23 Uppsala Sweden Abstract Nine psychotic patients under continuous oral treatment with haloperidol were randomly given a test dose of 1.5–5 mg haloperidol orally and/or intravenously. Serum levels of haloperidol were determined by high performance liquid chromatography and serum concentration data obtained were submitted to pharmacokinetic analysis. The steady state concentration ratio between blood and plasma was determined and found to be 0.79±0.03. The blood clearance was then calculated to be 550±133 ml/min. The mean hepatic extraction ratio was intermediate (0.37). Consequently, for a drug mainly eliminated by hepatic metabolism like haloperidol, the total blood clearance and the extent of oral bioavailability can be affected by changes in hepatic blood flow, hepatic enzyme activities and drug binding. During continuous oral treatment with haloperidol, however, it can be shown that changes in the total metabolic capacity of the liver due to hepatic enzyme induction or inhibition should be important for the therapeutic effects of haloperidol. The volume of distribution at steady state ( V dss) was large (7.9±2.5 l/kg). The terminal half-life was 18.8 h after intravenous and 18.1 h after oral administration. The oral bioavailability (0.60±0.18) were in accordance with previous results in healthy subjects. A mean lag time after oral dose was 1.3±1.1 h and a longer absorption half-life (1.9±1.4 h) was found in the patients compared with healthy volunteers.
Psychopharmacology – Springer Journals
Published: Apr 1, 1987
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