Abstract
The pharmacokinetics of pafenolol were evaluated in 12 healthy subjects after administration of three single IV doses (5, 10, and 20mg) and three oral single doses (25, 50, and 100mg). The drug was discontinuously absorbed. A first peak was observed 0·5 to 1·5h after dosing and a second higher maximum concentration was noted 3 to 5h 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 100mg dose, i.e., an increase of about 70 per cent (p < 0·05). The half‐life of distribution varied between 5 and 6min and the apparent volume of distribution (V~z~) was about 1·11 kg^−1^. The distribution was linear in the IV dose range studied. Total body clearance was about 300ml 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 < 0·05) by increasing the dose from 5 to 20mg IV possibly because of reduced renal elimination. Mean terminal t~1/2~ of the IV dose was ∽ 3·5h. The corresponding t~1/2~ of the oral dose was ∽ 6h indicating absorption rate‐limited kinetics of the oral dose.