It can be expected that combination of low doses of TRM and VEN could potentially be feasible and relatively safe in cases with acute pain with co-existing depression, however, further investigations are needed.

The bioavailability of drotaverine (CAS 14009-24-6) was investigated after oral administration of a drotaverine capsule preparation (20 mg Droxa mite) and compared to that of a reference tablet preparation. The preparations were investigated in 23 healthy volunteers, aged between 20 and 27 years, according to a randomised two-way, cross-over design in the fasted state. Blood samples for determination of drotaverine plasma concentrations were collected at pre-defined time points up to 30 h following drug administration. A washout period of two weeks separated both treatment periods. Drotaverine plasma concentrations were determined by means of a validated HPLC method (UV detector, imipramine HCl salt as an internal standard). The limit of detection was 6 ng/ml. Values of 1593.92 +/- 949.70 ng x h/l (95% confidence interval (CI): 1183.20-2004.60) for the test and 1705.48 +/- 737.78 ng x h/l (95% CI: 1386.40-2024.50) for the reference preparation AUC(0-infinity) demonstrate a nearly identical extent of drug absorption. Maximum concentrations--Cmax of 121.89 +/- 37.03 ng/ml (95% CI: 104.05-139.80) and 121.85 +/- 37.97 ng/ml (95% CI: 107.09-135.74) and time to reach maximum plasma concentration--Tmax of 1.29 +/- 0.42 h (95% CI: 1.11-1.48) and 1.14 +/- 0.34 h (95% CI: 0.99-1.29) achieved for the test and reference preparations did not differ significantly. The relative bioavailability (AUC(0-infinity) ratio test/reference) and Cmax ratio test/reference were 103.15% (90% CI: 81.68-124.60) and 103.74% (90% CI: 94.10-113.38), respectively. AUC was calculated using two different methods. There were no significant differences between the obtained values. Since the 90% CI for both, AUC and Cmax ratios were within the 80-125% interval proposed by the European Agency for the Evalution of Medicinal Products (CPMP) and the Food and Drug Administration, it is concluded that the new drotaverine capsule formulation is therapeutically equivalent to the conventional formulation for both, the extent and the rate of absorption after single dose administration in healthy volunteers.

Background: To determine the stability of fludarabine phosphate in concentrate in glass containers and diluted with sodium chloride 0.9% in polyethylene (PE) bags. Material and methods: Solutions of fludarabine phosphate 25 mg/ml (concentrate) in glass containers (n = 6) were opened and stored at refrigerator temperature (2-8°C) and at room temperature (15-25°C). Another six solutions of fludarabine phosphate were diluted in NaCl 0.9% and stored in PE bags in the same conditions (2-8°C and 15-25°C). Samples of each solution from the 12 containers were analysed for fludarabine phosphate concentration initially and after 0.5, 1, 1.5, 2, 2.5, 3, 13 and 15 days of storage. Samples were assayed by a high performance liquid chromatographic (HPLC) method with ultraviolet detection (λ = 265 nm) to determine the fludarabine phosphate concentration at each time of sampling. Results: The concentration of fludarabine phosphate at each sampling time in the analysed solutions remained within 93.3-102.0% of the initial concentration, regardless of the storage temperature and container. Conclusions: Fludarabine phosphate, both undiluted in glass containers and diluted with NaCl 0.9% in PE bags, remains stable (< 10% degradation) for at least 15 days at room and refrigerator temperature.

Using a rabbit model, there is no evidence that the combined administration of tramadol and venlafaxine may increase the plasma exposure of tramadol and therefore increase the risk of serotonin syndrome.

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