Pharmacokinetics of pafenolol after i.v. and oral administration of three separate doses of different strength to man.

The pharmacokinetics of pafenolol were evaluated in 12 healthy subjects after administration of three single IV doses (5, 10, and 20 mg) and three oral single doses (25, 50, and 100 mg). The drug was discontinuously absorbed. A first peak was observed 0.5 to 1.5 h after dosing and a second higher maximum concentration was noted 3 to 5 h after the administration in the majority of the experiments. The mean systemic availability increased from 27 +/- 5 per cent for the oral 25 mg dose to 46 +/- 5 per cent for the 100 mg dose, i.e., an increase of about 70 per cent (p less than 0.05). The half-life of distribution varied between 5 and 6 min and the apparent volume of distribution (Vz) was about 1.11 kg-1. The distribution was linear in the IV dose range studied. Total body clearance was about 300 ml min-1. About 50 per cent of the systemically available dose was excreted unchanged via the kidneys. Total body clearance decreased by about 13 per cent (p less than 0.05) by increasing the dose from 5 to 20 mg IV possibly because of reduced renal elimination. Mean terminal t1/2 of the IV dose was approximately 3.5 h. The corresponding t1/2 of the oral dose was approximately 6 h indicating absorption rate-limited kinetics of the oral dose.