Pharmacokinetics of oxiracetam in patients with renal impairment after a 800 mg single oral dose

The pharmacokinetics of oxiracetam in patients with renal impairment were investigated after administration of a 800 mg single oral dose of oxiracetam. The renal insufficiency was estimated on the basis of the creatinine clearance (CLcr) which ranged from 9 to 95 ml/min among the 20 patients. In plasma, the terminal elimination half-life (T1/2) ranged from 10.6 to 68.1 h, the highest T1/2 corresponding to the patients with a high degree of renal impairment. In urine, the amounts of oxiracetam excreted during the 48 h postdosing represented 8.3 to 82.6% of the dose. They were lower in patients with a high degree of renal impairment. The correlations between the total clearance of oxiracetam, the renal clearance, the terminal apparent elimination rate constant in plasma, and CLcr were estimated by linear regression analysis. The correlation coefficients were 0.916, 0.985 and 0.803 respectively. The apparent volume of distribution of the central compartment V(1) and the total volume of distribution at the steady-state V(SS) were not dependent on the degree of renal impairment. The mean values±SD were 25.9±13.0 litres and 48.3±21.5 litres respectively. Oxiracetam concentrations in plasma of patients were estimated for repeated administration of 800 mg of oxiracetam. The estimations showed that the steady-state concentrations would be obtained after 6–10 days of repeated administration for patients whose CLcr is 9–15 ml/min and 3–5 days for patients with CLcr between 15 and 40 ml/min. The dosage of oxiracetam in renal insufficient patients was evaluated in order to reach a mean steady-state concentration level of oxiracetam in plasma close to that in patients with normal renal function. For patients with CLcr between 40 and 60 ml/min, the adjusted daily dose would be 50% of the dose given to a patient with normal renal function. For patients with CLcr between 15 and 40 ml/min, the adjusted daily dose would be 25% of the dose given to a patient with normal renal function. For patients whose CLcr was below 40 ml/min, one daily administration in agreement with the dosage reduction, could be given.