Pharmacokinetics and acute toleration of the beta-carboline derivative abecarnil in man.
Plasma levels of the beta-carboline, abecarnil (isopropyl 6-(benzyloxy)-4-(methoxymethyl)-9H-pyrido [3,4-b]indole-3- carboxylate, ZK112119) which is presently under development as an anxiolytic, were measured by HPLC with fluorescence detection in six healthy male volunteers given 30 micrograms/kg i.v. and 5 and 10 mg p.o. Following i.v. injection, plasma levels declined biphasically with half-lives of 6 min and 3.4 h. The total clearance was 13 ml/min/kg. After oral administration, maximum concentrations were reached after 2 h. The bioavailability was approximately 60%. The terminal half-life after p.o. administration was 7 h. No clinically relevant changes in ECG, vital signs or standard laboratory measurements occurred. Eight different adverse reactions were noted by the subjects. The most frequently reported side-effects were tiredness, dizziness, unsteady gait and lack of concentration.
Krause
W
W
Research Laboratories of Schering Aktiengesellschaft, Berlin, Germany.
Schütt
B
B
Duka
T
T
D000328:Adult; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002243:Carbolines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004562:Electrocardiography; D006207:Half-Life; D006801:Humans; D008297:Male; D011674:Pulse / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D013050:Spectrometry, Fluorescence
D014151:Anti-Anxiety Agents; D002243:Carbolines; C062769:abecarnil