No abstract

AimsTo compare the pharmacokinetic profile of a new modified release formulation of tramadol (Tramadol LP 200 mg, SMB Technology, Marche-en-Famenne, Belgium) with that of an immediate release capsule (Topalgic® 50 mg, Grünenthal, Aachen, Germany) after single and multiple dosing and to assess the potential effect of food on its relative bioavailability. MethodsThe first study had an open, single-dose, three-treatment, three-period, six-sequence, randomised, crossover design with at least a five-day wash-out. The second study had an open, steady-state, two-treatment, two-period, two-sequence, randomised crossover design with at least a seven-day wash-out. Both studies contained 30 healthy subjects. Both enantiomers of tramadol and O -demethyl-tramadol (the only active metabolite of tramadol) were assayed in the plasma using an LC-MS/MS method. AUC • , AUC t , C max , T max , and T 1/2 were estimated. Statistical analysis was performed using univariate ANOVA , the Wilcoxon nonparametric method or Friedman's nonparametric ANOVA where appropriate. ResultsTramadol had a significantly lower C max and longer Tmax than the conventional formulation. Thus, the mean ( ± sd) C max of tramadol were 646 ± 192 and 300 ± 94 ng ml -1 for Topalgic® 4 ¥ 50mg and Tramadol LP 200 mg, respectively (95% confidence interval on the difference expressed as a percentage 42-51). AUC of tramadol from both formulations was comparable (similar AUC • and AUC t ). Thus, the mean AUC • of ( + /-)tramadol obtained after multiple dosing were 4611 ± 1944 and 5105 ± 2101 ngh ml -1 after Topalgic® 4 ¥ 50mg and Tramadol LP 200 mg, respectively (95%CI 102-123%). We also demonstrate that the pharmacokinetics of the drug are not influenced by the intake of food. Thus, the mean AUC • of ( + /-) tramadol were 5444 ± 1637 and 5169 ± 1580 ngh ml -1 after Tramadol LP 200 mg given in the fasting and fed states, respectively (95%CI = 88-103%). ConclusionsThe new sustained release form of tramadol exhibits adequate proper ties for once a day administration. Furthermore, its pharmacokinetic profile is not affected by the intake of food. Tramadol sustained release pharmacokineticsBr J Clin Pharmacol 57 :3 271

Long-term treatment with tramadol LP once daily is generally safe in patients with osteoarthritis or refractory low back pain.

Bioequivalence of a newly developed semi-solid formulation (Lidose) of fenofibrate (CAS 49562-28-9), and a reference, micronized formulation of fenofibrate was investigated in two randomised, open-label clinical studies with a crossover design. Both studies involved two distinct groups of 24 healthy volunteers. Doses of 67 mg and 200 mg, respectively, were used in study 1 and study 2. On day 1, a single oral dose was administered to all subjects, using one of the two formulations to be compared. Single oral dosing with the other formulation occurred after a washout period of at least 8 days. Blood samples were taken after each dosing for measurement of plasma fenofibric acid concentrations by high-performance liquid chromatography (HPLC) combined with fluorescence detection, and plasma pharmacokinetic parameters were determined. No statistically significant differences were noted for Cmax, Tmax, AUC0-t and AUC0-variation of between subjects treated with the new formulation and those receiving the reference formulation. Side effects were mild and not significantly different between the two fenofibrate preparations. These two studies based on validated methods demonstrate that the new and the reference fenofibrate formulations are bioequivalent when administered at the two doses studied.

No abstract