Pharmacokinetics and safety of deramciclane during multiple oral dosing

Deramciclane is a new putative non-benzodiazepine-type anxiolytic compound. It is a selective serotonin 5-HT2A and 5-HT2C receptor antagonist and has also inverse agonist properties. The aim of this study was to reveal the ph armacokinetics and tolerability of deramciclane during repeated oral dosing in healthy male volunteers. Subjects . material and methods: A randomized double-blind, placebo-controlled design was used. The study had three conse cutive groups that received first a single oral dose of 10, 30 and 60 mg of deramciclane followed by twice a day administration for seven days. The to tal number of subjects was 28. The pharmacokinetic parameters were calculat ed for a single dose and after repeated administration. Tolerability was as sessed by monitoring safety laboratory variables, electrocardiogram, heart rate, blood pressure and adverse events. Results: The steady-state was reac hed during the seven-day administration. The pharmacokinetics of deramcicla ne was dose-proportional at steady-state at each dose level. Deramciclane a ccumulated about three-fold during repeated administration. The relative bi oavailability of deramciclane increased about 1.4-fold compared to that of a single dose at each dose level. The mean elimination half-life of deramci clane for 10, 30 and 60 mg doses prolonged from 24.3, 20.9 and 22.9 h after a single dose to 30.5, 25.6 and 28.7 h at steady-state, respectively. Only few adverse events were reported, all mild and transient in nature. The mo st frequently re ported adverse drug reactions were tiredness and headache. There were no deramciclane-induced changes in the clinical chemistry or he matology variables, blood pressure, heart rate or in electrocardiogram. Con clusions In conclusion, the pharmacokinetics of deramciclane is linear over the dose range of 10 - 60 mg at steady-state. The slight non-linearity wit hin the dose levels during repeated administration of seven days was regard ed as clinically irrelevant. Deramciclane was safe and well tolerated up to doses of 60 mg b.i.d. for seven days.