Pharmacokinetics of nortilidine and naloxone after administration of tilidine/naloxone solution or tilidine/naloxone sustained release tablets.

ABSTRACT

Valoron N is a compound which consists of the prodrug tilidine (CAS 20380-58-9), from which the active metabolite nortilidine is formed by demethylation in the liver, and the opiate antagonist naloxone (CAS 465-65-6), which prevents the abuse of the analgesic by opiate dependents. The pharmacokinetics of nortilidine and naloxone were studied in 18 male healthy subjects after oral application of tilidine/naloxone solution or tilidine/naloxone retard tablets, respectively. The following report gives the results on investigations of a) dose linearity after application of 25 mg, 50 mg and 100 mg Valoron N solution, b) dose equivalence of Valoron N solution (4 x 50 mg tilidine) and Valoron N retard tablets (2 x 100 mg tilidine) under steady state conditions, and c) the equivalence of different dose strengths of Valoron N retard tablets (50 mg, 100 mg, 200 mg tilidine/tablet). The results obtained in these studies demonstrate a dose linear kinetic for nortilidine after the application of 25 mg to 100 mg tilidine. Furthermore, there is dose equivalence between the tilidine/naloxone solution and tilidine/naloxone retard tablets, which permits the replacing of the solution with the retard tablets. Because of the equivalence of different dose strengths of Valoron N tablets, patients are able to exchange low dosed Valoron N retard tablets for higher-dosed ones (50 mg, 100 mg and 200 mg tilidine/tablet), if necessary. With their constant release of tilidine and the possibility for individual dosage, the retard tablets are efficient analgesics that improve pain therapy considerably for patients with chronic pain.