[Clearance concept applied to pharmacokinetics: 2. Experience with tolamolol (beta-blocking agent) in renal...

Tolamolol is subject to first-pass metabolism and is eliminated from the body almost entirely by biotransformation. Its major metabolite in plasma (4-hydroxy-tolamolol) is biologically active and may contribute to the pharmacological effect of the drug. The effect of renal failure on the behaviour of the parent compound and of its metabolite was studied by comparing their kinetics in normal volunteers and in patients with severe renal insufficiency. Tolamolol was given orally to all subjects at a 100 mg dose. Renal failure was found to be associated with a marked increase of the areas under the plasma concentration-time curves of the parent compound, whereas its half-life of elimination was not markedly influenced. The behaviour of tolamolol in patients with renal failure was analysed using the clearance approach. From this analysis it appears that the presystemic biotransformation of tolamolol is decreased in renal failure.