Kinetics of idaverine in healthy male subjects after single dose oral and intravenous administration.

The kinetics of idaverine was studied in an open, cross-over, partially randomized design after single oral (2 mg) and intravenous (1 and 2 mg doses to 12 healthy male subjects. In the first session, the volunteers were administered 1 mg idaverine by constant intravenous infusion during 45 min. The treatments in the second and third sessions were given according to a cross-over design, randomized in blocks of six for each session (2 mg either orally or by intravenous infusion during 45 min). The washout period between the sessions was at least 1 week. Plasma, urine and faeces were analysed for idaverine and its pharmacologically active metabolite N-desmethylidaverine by gas chromatography with nitrogen flame ionisation detection. After intravenous administration, the MRT was on average 2 hours and the mean CLS was about 900 ml.min-1. CLR is about twice the glomerular filtration rate, suggesting net tubular secretion of idaverine. The AUC and the cumulative urinary and faecal excretion values gave no indication of dose-disproportionality within the range of 1 and 2 mg administered intravenously. Maximum plasma levels of 1-3 ng.ml-1 were reached between 0.5 hours and 3 hours after oral dosing. The MRT was 4.4 hours. Systemic availability was about 29%. N-desmethylidaverine was barely detectable in plasma after all doses. Idaverine was well tolerated, only a small increase in heart rate was observed.