title: 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.
authors.forename: U
authors.initials: U
authors.lastname: Brennscheidt
authors.forename: K U
authors.initials: KU
authors.lastname: Seiler
authors.forename: P
authors.initials: P
authors.lastname: Thomann
mesh_terms: D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000009:adverse effects / Q000493:pharmacokinetics*; D009292:Narcotic Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics*; D012044:Regression Analysis; D013993:Tilidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D009292:Narcotic Antagonists; D009270:Naloxone; C062490:nortilidine; D013993:Tilidine