Biodisposition of tertatolol in man: a review

Tertatolol is rapidly (tmax: 1.25 h) and totally absorbed by the gastro-intestinal tract with a low presystemic metabolism, and the bioavailability (60%) is not affected by food intake. Although clearance is low (130 ml/min), half-life is short (3 h) due to a restricted volume of distribution. Tertatolol is extensively metabolized (99%) to 9 metabolites with three equally important pathways, sulfoxidation, hydroxylation and conjugation. The half-life is not altered in hypertensive patients. It is increased in the elderly (7 h) and in patients with renal failure (9 h, irrespective of creatinine levels). However, considering the once-daily regimen, the recommended dose (5 mg/24 h) does not need to be altered in these patients. In hepatic disease, the modifications of pharmacokinetic parameters correlate with the severity (t1/2 = 14.5 h in the severe group). Taking into account the extensive metabolism of the drug, this justifies halving the dose in patients with cirrhosis and prothrombin time less than 70%. The kinetics are linear over a 10-fold dosage range and, after repeated dosing, there is no accumulation. Despite the short half-life, and because of a flat plasma level response curve, beta-blockade continues for 24 h following a 5-mg dose.