Determination of fendiline and gallopamil by capillary isotachophoresis.

Capillary isotachophoresis was applied for the determination of fendiline and gallopamil--calcium antagonists--in serum. The cationic electrolyte system containing Na+ with acetic acid as a counter constituent was used as a leading electrolyte with the pH 4.7 and the terminating electrolyte was beta-alanine. Most of the proteins were precipitated with methanol, ethanol and dimethylketone. The lowest limits of quantitation were obtained for the pretreatment of serum with methanol. The recoveries of both compounds varied from 91.3 to 97.5%. The relative standard deviations varied from 0.6 to 7.7%.

Determination of fendiline in human plasma by means of capillary gas chromatography and nitrogen-phosphorus selective detection.

A sensitive and specific method for the determination of fendiline in human plasma is presented. Fendiline was extracted from human plasma after the addition of phosphate buffer two times with 4 ml of n-hexane. The organic phase was separated and evaporated to dryness at 40 degrees C under a stream of nitrogen. The residue was dissolved and an aliquot was injected into the gas chromatograph. Chromatographic separation was performed with a DB-1 column with helium as carrier gas. Nitrogen-selective detection was performed. Quantification was performed with the signal output. The limit of detection was 1 ng/ml of plasma.

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.