Absolute bioavailability of amezinium. A cross-over study after i.v. and p.o. application

The absolute bioavailability and pharmacokinetics of 4-amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (amesiniummetilsulfate, LU 1631, Regulton), in the following briefly called amezinium, were examined following i.v. injection (10 mg) and single p.o. doses administered to eight healthy male volunteers. After i.v. injection plasma levels of amezinium were described by a tri-exponential function and the mean half-lives of the three phases were 0.08, 1.5 and 14 h, respectively. The volume of distribution at steady state ranged between 201 and 476 1. After p.o. doses of tablets, absorption of the drug obviously commenced immediately after dosing. After 0.5 h the absorption took place more rapidly and peak plasma levels between 31 and 61 ng/ml were reached after 1.2 to 2.4 h. The mean terminal half-life in plasma was 13 h after p.o. doses. 77% of the i.v. dose was excreted unchanged in the urine over 48 h; the mean excretion after the p.o. dose was 32%. Within the first 7 h the renal clearance of amezinium was considerably higher than afterwards. The mean absolute bioavailability determined by means of the area under the plasma concentration-time curve (AUC) was 53% and ranged between 40% and 74%.