A phase IV, two-armed, randomized, cross-over study comparing compliance with once-a-month administration of vitamin D3 to compliance with daily administration of a fixed-dose combination of vitamin D3 and calcium during two 6-month periods.

UNLABELLED: In a randomized, cross-over study, once monthly administration of vitamin D3 was preferred over a once daily administration of a fixed-dose combination of vitamin D3 and calcium, with a better compliance but without any significant difference in the increase in vitamin D levels. INTRODUCTION: The aim of the present study was to compare a once-monthly administration of vitamin D3 to a daily administration of a fixed-dose combination of vitamin D3 and calcium during two treatment periods of 6 months. METHODS: One hundred volunteers aged 50 years old or older were randomized to receive either one drinkable ampoule containing 25,000 IU vitamin D3 (D-Cure®, SMB) once monthly (group VD) or one chewable tablet containing 1000 mg calcium carbonate + 800 IU vitamin D3 (Steovit Forte®, Takeda) once daily (group VDCa) during 6 months. After the first 6 months of treatment, the groups were reversed according to the randomized cross-over design. Treatment compliance (i.e. the primary outcome), preference, acceptability and vitamin D levels and adverse events were all collected. RESULTS: For the two periods, the patients had a significantly higher compliance in the VD group than in the VDCa group (p < 0.0001). During the study, 50 (56.8 %) patients preferred the VD treatment, 16 (18.2 %) patients preferred the VDCa, and for 22 (25.0 %) patients, neither treatment was preferred. At the end of the first 6 months of treatment, the mean (SD) increase of 25(OH)D was 6.57 ng/mL (8.19) in the VD group and 3.88 ng/mL (10.0) in the VDCa group (p = 0.16 between groups). CONCLUSION: In this study, a once-monthly administration of vitamin D3 was preferred over a once-daily administration of a fixed-dose combination of vitamin D3 and calcium, with a better compliance but without any significant difference in the increase in vitamin D levels.

Treatment of alcoholic polyneuropathy with vitamin B complex: a randomised controlled trial.

AIMS: To evaluate the therapeutic efficacy and safety of BEFACT Forte 'new formulation' and BEFACT Forte 'old formulation' in the treatment of sensory symptoms of alcoholic polyneuropathy. METHODS: A multi-centre, randomised, double-blind, placebo-controlled study was conducted on 325 patients with sensory symptoms and signs of alcoholic polyneuropathy. Patients were randomised to the 'old formulation' (i.e. vitamins B1, B2, B6, and B12), 'new formulation' [i.e. identical to the 'old formulation' with additional folic acid (vitamin B9)], or placebo in a 1:1:1 ratio. One tablet of the study medication ('new formulation' or 'old formulation') or placebo was taken orally, three times a day, over a 12-week treatment period. RESULTS: Therapeutic efficacy was assessed in 253 patients by measuring vibration perception threshold (biothesiometry), intensity of pain, sensory function, co-ordination, and reflex responses. Patients treated with the 'new formulation' or 'old formulation' showed significant improvement in the primary efficacy endpoint (vibration perception threshold at the big toe) and secondary efficacy endpoints in comparison to placebo. The active treatment groups were comparable to placebo in terms of safety. CONCLUSIONS: A specific vitamin B complex (with and without folic acid) significantly improved symptoms of alcoholic polyneuropathy over a 12-week treatment period.

Pharmacokinetic evaluation of a new oral sustained release dosage form of tramadol.

AIMS: To 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. METHODS: The 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 infinity, AUCt, Cmax, Tmax, and T1/2 were estimated. Statistical analysis was performed using univariate anova, the Wilcoxon nonparametric method or Friedman's nonparametric anova where appropriate. RESULTS: Tramadol had a significantly lower Cmax and longer Tmax than the conventional formulation. Thus, the mean (+/- sd) Cmax of tramadol were 646 +/- 192 and 300 +/- 94 ng ml-1 for Topalgic 4 x 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 infinity and AUCt). Thus, the mean AUC infinity of (+/-)tramadol obtained after multiple dosing were 4611 +/- 1944 and 5105 +/- 2101 ngh ml-1 after Topalgic 4 x 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 infinity 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%). CONCLUSIONS: The new sustained release form of tramadol exhibits adequate properties for once a day administration. Furthermore, its pharmacokinetic profile is not affected by the intake of food.