[Plasma level and action of sotalol-HCL on the ECG interval after parenteral administration in healthy subjects]. / Plasmaspiegel und Wirkung von Sotalol-HCl auf EKG-Zeitintervalle nach parenteraler Applikation an gesunde Probanden.

Sotalol (Sotalex; Sotacor) is a beta-blocker with additional class III antiarrhythmic activity. In this study two intravenous doses of 1.5 mg/kg and 2 mg/kg body weight were administered in 8 healthy volunteers in order to determine the pharmacokinetics and ECG intervals. After a short-term infusion (5 min) plasma levels and the relevant pharmacokinetic parameters were determined. The ECG parameters (QRS, PQ, QT, QTc), blood pressure, heart rate and tolerability were also evaluated. A correlation between the plasma concentration of sotalol, the decrease in heart rate and a prolongation of the real QT interval was found for both dose levels and for a period of 2 h after administration. A prolongation of the QTc-time could only be statistically confirmed for the higher dose. No differences in pharmacokinetic parameters were observed between the two doses.

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.

[Relative bioavailability of paracetamol from tablets and suppositories as well as of paracetamol and codeine in a combination tablet]. / Relative Bioverfügbarkeit von Paracetamol aus Tabletten und Zäpfchen sowie von Paracetamol und Codein aus einer Kombinationstablette.

Eight healthy male volunteers took part in this study to determine the relative bioavailability of Treuphadol oblong tablets (500 mg paracetamol), Treuphadol Plus oblong tablets (500 mg paracetamol, 30 mg codeine phosphate) and Treuphadol suppositories (750 mg paracetamol) against commercial tablets (500 mg paracetamol). Plasma levels of paracetamol and codeine, plus saliva levels of paracetamol for the two paracetamol only formulations, were determined by HPLC and the pharmacokinetic parameters established. The AUC data for paracetamol showed that all four preparations were bioequivalent. The saliva levels of paracetamol demonstrated a good correlation to the corresponding plasma levels. The pharmacokinetic data of codeine from the Treuphadol Plus tablet were compared with corresponding data from the literature. The bioequivalence of codeine when based on this comparison can also be assured.

An early phase I study to determine the tolerance, safety and pharmacokinetics of idebenone following multiple oral doses.

Ten healthy male volunteers participated in this Phase I multiple dose study with CV-2619 (6-[10-hydroxydecyl]-2,3- dimethoxy-5-methyl-1,4-benzoquinone, idebenone). Each volunteer received single oral doses of 100 mg CV-2619 on study days 1 and 35, and during days 2 to 34, 300 mg daily in three divided doses. Blood and urine samples were collected for pharmacokinetic analysis of CV-2619 and its two major metabolites. CV-2619 was well tolerated with regard to the subjective and objective assessments made during the study. There were no changes in clinical laboratory values which could be directly attributed to the administration of CV-2619. The elimination of CV-2619 appeared to be biphasic with a mean terminal elimination half-life of 18 h. Levels of metabolites in serum were too low to provide adequate description of their elimination kinetics. CV-2619 and its metabolites showed no tendency to accumulate over the 35-day period.