Comparative bioavailability of two tablet preparations of diltiazem in healthy volunteers.

Comparative bioavailability of two formulations of diltiazem (Dilzene, CAS 42399-41-7), a calcium antagonist, was evaluated on 10 healthy volunteers (5 males and 5 females) in a cross-over study. A single dose of 120 mg of diltiazem was administered to the volunteers in the form of either two 60-mg tablets or a 120 mg controlled-release tablet. Plasma concentrations of diltiazem over a 24-h time interval were determined by HPLC analysis. Results of this investigation demonstrate that the controlled-release formulation of diltiazem has a lower Cmax value when compared to the 60 mg conventional tablet formulation, but a longer tmax and a superimposable AUC.

Pharmacokinetics and tissue distribution of ofloxacin in human subjects during a multiple dose regimen.

The pharmacokinetics of ofloxacin was studied in normal male volunteers selected from a student population. The aim of this study was to ascertain whether ofloxacin accumulated in plasma after administering six oral doses of the drug. The drug was administered in 300 mg tablets at intervals of 12 h for a total period of 72 h. The results clearly demonstrated that a modest accumulation of ofloxacin was observed between the first and second oral intake of the drug (R = 1.4); thereafter a steady-state plasma concentration was maintained at all time periods tested during the study. Furthermore, there was a broad fluctuation of approximately 80% between the Cmax and Cmin in the plasma levels of the drug during a 12-hour dosing interval. Hence demonstrating that a constant dose, repeatedly administered at a constant time interval of 12 h, ensured a broad range of concentrations of ofloxacin plasma, bile and other tissues which should favour the therapeutic success of the drug. There was agreement between the results of these studies and those in hospitalized patients suffering from severe infections. Analysis of ofloxacin after multiple dosing regimens in these patients showed measurable concentrations of the drug in the various tissues examined; hence suggesting a relative good bioavailability of the drug, which presumably reflected the high degree of success rates in these patients.

Safety profile of ofloxacin: the Italian data base.

In clinical trials performed in Italy, 2,003 patients, suffering from various infectious diseases, have so far been treated with ofloxacin. In most cases dosages of 200 mg, 300 mg or 400 mg b. i. d. have been used. In all, 130 adverse reactions have been recorded in 116 patients (5.8%): gastrointestinal events (mostly nausea, vomiting and gastric pain) in 4.8% of the patients, neurological events (mostly headache and insomnia) in 0.7%, cutaneous reactions in 0.4% and others in 0.5% cases. The drug-event causal relationship was assessed by the investigators as unlikely in 5.0% of the events, as possible in 47.1%, as probable in 31.4% and as almost certain in 16.5%. The severity of adverse reactions was judged as mild in 55% of the cases, as moderate in 38% and as severe in 7%. In 30 patients (1.5%), treatment was discontinued because of occurrence of side effects. Abnormal laboratory values probably related to treatment were reported in 25 patients (2.1%). Ofloxacin is well tolerated and shows a safety profile comparable with that of the best tolerated oral antibacterials.