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Lorcainide disposition kinetics in arrhythmia patients
Author(s) -
Kates Robert E,
Keefe Deborah L,
Winkle Roger A
Publication year - 1983
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1983.4
Subject(s) - volume of distribution , metabolite , pharmacokinetics , oral administration , disposition , distribution (mathematics) , dosing , active metabolite , steady state (chemistry) , chemistry , chromatography , pharmacology , medicine , mathematics , psychology , social psychology , mathematical analysis
Lorcainide disposition kinetics were studied after intravenous and oral administration to patients with ventricular arrhythmias. After intravenous doses ranging from 100 to 200 mg, blood samples were drawn and plasma was analyzed for lorcainide concentration by high‐pressure liquid chromatography. A three‐compartment model was used to fit the data. The model‐independent calculated values for clearance, steady‐state volume of distribution, and terminal half‐life were 14.4 ± 3.28 ml/min/kg, 6.33 ± 2.23 l/kg, and 7.8 ± 2.2 hr. After nine doses of oral lorcainide (100 mg every 12 hr) blood samples were drawn and analyzed for lorcainide and its active metabolite, norlorcainide. The lorcainide and norlorcainide half‐lifes were 9.6 ± 2.8 and 26.8 ± 8.2 hr. Mean steady‐state level of norlorcainide was 2.2 ± 0.9 times the level of lorcainide. The data suggest that the clearance of lorcainide decreases with time during long‐term dosing. Clinical Pharmacology and Therapeutics (1983) 33, 28–34; doi: 10.1038/clpt.1983.4