Pharmacokinetics of xamoterol after intravenous and oral administration to patients with chronic heart failure

Summary

The pharmacokinetics of xamoterol, a β-adrenergic partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 8 cardiac failure patients (NYHA Class II) of mean age 62 years.

After i.v. dosing, the elimination half-life was 7.4±0.4 h, the total body clearance was 228±30 ml·min⁻¹ and the volume of distribution at steady-state was 56±91. 72.5±4.3% of the dose was recovered unchanged in urine. After the oral dose, the absolute bioavailability of xamoterol was shown to be 5.9%. Peak plasma concentrations occurred 1 to 2.5 h after the oral dose. The apparent elimination half-life was significantly longer after oral doses (16±2 h) compared to that observed after an intravenous dose. Renal clearance of xamoterol exceeded glomerular filtration rate as measured by creatinine clearance.

The pharmacokinetics of xamoterol in cardiac failure patients with good renal function (creatinine clearance >90 ml·min⁻¹) were similar to published data in young healthy male volunteers.