Pharmacokinetics of oral talinolol following a single dose and during steady state in patients with chronic renal failure and healthy volunteers

Objective: The objective of this study was to investigate the effect of renal impairment on the pharmacokinetics of the selective PI-receptor antagonist talinolol. Methods: Pharmacokinetic data were obtained in 12 healthy volunteers, 12 patients with renal impairment and 8 patients with terminal renal insufficiency after the oral administration of 100 mg talinolol and under steady state conditions (100 mg talinolol daily). Concentrations of talinolol in plasma, urine and dialysate during hemodialysis were measured with a validated HPLC-method. Results: Talinolol is absorbed quite rapidly from the gastrointestinal (t(max) 2.5 - 4 h). Steady state conditions were reached within 3 - 4 days depending on renal function. The calculated mean elimination half-life (t(1/2z)) in healthy volunteers (11 male, 1 female) was about 12 h. After an oral dose of 100 mg, about 55% of the bioavailable talinolol is eliminated unchanged in the urine. This fraction is reduced to 25% in patients with moderate to severe renal failure. A strong correlation was found between the renal elimination of talinolol and creatinine clearance. In patients with renal failure, the delayed elimination leads to an increase in t(1/2z) and to a decrease in the apparent total body clearance. Steady state trough levels (c(min)(ss)) in these patients are about 2.2-fold higher than in volunteers. The hemodialysability of talinolol was low. Conclusion: The disposition of talinolol shows a strong dependence on the renal function. On the basis of the kinetic data for talinolol, dose reductions of 30 - 50% are recommended in subjects with moderate to severe renal impairment.