Tolerance and pharmacokinetics of oral fendiline.

Two studies with healthy volunteers were carried out to correlate safety with pharmacokinetics of the calcium antagonistic drug N-(3,3-diphenylpropyl)-(1-phenylethyl)-amine (fendiline, Sensit) after single and multiple oral doses. In the first study single doses of 200, 400, 600, 800, 1000, and 1200 mg of fendiline hydrochloride were administered to 6 subjects per dose level. 3 additional subjects per dose level received placebo. No significant objective or subjective effects were noted in the dose range studied. The pharmacokinetic analysis revealed that doses higher than 800 mg were absorbed incompletely. In the second study initially 400 mg twice daily was given to 9 subjects. 3 additional subjects received placebo. Due to subjective intolerability (trembling, dizziness) after 5 days, the dose was reduced stepwise to 2 X 200 mg and was then continued for another 19 days. The pharmacokinetic evaluation revealed manifold interindividual differences in plasma levels for maximal concentrations (9-170 ng/ml) as well as for minimal concentrations (4-96 ng/ml). The absorption profile in both studies has linear and nonlinear components. Maximal plasma levels were reached after about 4 h. Terminal elimination half-lives were about 20 h.

[Treatment of Raynaud's syndrome with calcium entry blockers]. / Lechenie sindroma Reino blokatorami vkhoda kal'tsiia.

The authors have presented the results of a 14-day open randomized trial of the efficacy of 3 calcium inlet blocking agents: nifedipine, verapamil and phendilin in 61 patients with Raynaud's syndrome. In the group of patients receiving 30-80 mg of nifedipine (20) there was a significant decrease in the frequency and expression of Raynaud's syndrome attacks, a positive effect of varying degree was noted in 19 patients. The drug raised slightly the skin and muscular blood flow and skin temperature. The use of 120-360 mg of verapamil in 21 patients caused no significant inhibition of Raynaud's syndrome and rise of hemocirculation. Phendilin (150-300 mg) though being comparable with nifedipine in efficacy, often produced side-effects resulting in the drug cancellation (8 out of 20). The efficacy of the calcium inlet blocking agents, especially nifedipine, for therapy of Raynaud's syndrome was emphasized.

[Fendiline and isosorbide dinitrate in coronary heart disease (author's transl)]. / Fendilin und Isosorbiddinitrat bei koronarer Herzkrankheit. Gekreuzte Doppelblindvergleichsstudie.

In a randomized cross-over double-blind study of 30 out-patients with true angina the efficacy of fendiline and isosorbide dinitrate (ISDN) was compared. In randomized order the patients daily took either 3 X 50 mg fendiline or 2 X 20 mg ISDN (plus 1 placebo tablet). Each treatment period lasted for six weeks. Ergometric tests were performed at the onset of the study and at intervals of three weeks. The main criterion for the efficacy of the treatment was a change in S-T segment (at 0.06 s after the QRS). With either drug there occurred a statistically significant reduction in S-T depression and in the frequency of anginal attacks during the first treatment period. But there was a difference between the two drugs: Whereas with ISDN a marked reduction in S-T segment depression was observed after three weeks, this effect slightly receded in the second part of the treatment period, while with fendiline the reduction in S-T depression continued over the entire treatment period. There was no significant difference between the two drugs as to side-effects or tolerance.