This paper reports the results of a pharmacokinetic study involving 24 healthy volunteers and designed to characterise the rate and extent of diclofenac absorption after the administration of a single dose of diclofenac (CAS 15307-86-5) potassium salt 50 mg in sachet (Voltfast) and tablet (Cataflam) formulations. Timed plasma concentrations of diclofenac during a 12-h-period after dosing were measured by means of HPLC with UV detection at 275 nm and a quantification limit of 10 ng/ml; the method was fully validated for pharmacokinetic purposes. These plasma concentrations were used to calculate Cmax, tmax, trapezoidal AUC0-t and AUC0-infinity and t1/2 by means of noncompartmental analysis. Cmax and tmax are the parameters expressing the rate of absorption, whereas the AUCs reflect the extent of absorption. The rate of absorption with the sachets proved to be very fast, reaching peak values at 10 min in seven subjects and at 15 min in the remaining subjects: mean time was 13.68 min, with concentrations at 5 min being 38% of Cmax. The average time to peak concentration with the tablets was 53.10 min. The extent of absorption of the sachets and tablets was similar, with AUC0-infinity values of respectively 1362 and 1214 ng.ml-1.h, and a 90% confidence interval 1.05-1.20. The highly soluble potassium salt of diclofenac was rapidly absorbed, especially in its sachet formulation, and thus appears to be an invaluable analgesic agent that is particularly useful for quick pain relief.

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Administration of lorazepam for preanaesthetic medication is generally expected to produce amnesic action. We conducted two studies to evaluate the relationship of plasma levels of lorazepam with its clinical effects. Forty patients, receiving 0.03 or 0.05 mg/kg lorazepam i.m. as preanaesthetic medication for various neurosurgical procedures, were asked 24 h after anaesthesia whether they could recall the insertion of the i.v. needle and a picture shown to them before induction of anaesthesia. Another 11 patients were given 0.03 mg/kg lorazepam i.v. and their degree of drowsiness was rated immediately before induction of anaesthesia. Plasma levels of lorazepam were measured by gas chromatography from samples drawn before induction of anaesthesia. No relationship between either the dose of lorazepam used or the plasma levels of lorazepam and the incidence of amnesia or the degree of drowsiness was observed. Three patients receiving 0.05 mg/kg of lorazepam i.m. had prolonged drowsiness, which made it difficult to check the patients' neurological condition after the operation. It is postulated that the unpredictable and variable central nervous system effects of lorazepam in neurosurgical patients may be due to differences in the capacity of lorazepam to penetrate the blood brain barrier.

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The clinical efficacy and safety of ibopamine and diuretic therapy were compared in a multicenter, multinational, parallel, positive-controlled, randomized, double-blind, 12-week study, involving 103 patients with mild CHF (NYHA Class II). Body weight, NYHA functional class, symptom assessment scores, laboratory blood tests, and exercise testing were evaluated at baseline at interim visits and at the end of 12 weeks. Clinical events were monitored throughout the study.There was no difference in any of the considered parameters between the two patient groups at baseline and at the end of the 12-week evaluation. A trend of improvement in clinical conditions that did not reach statistical significance was noted in each group throughout the study, as a probably "trial effect." Five patients on ibopamine had severe clinical events leading to drug discontinuation (CHF worsening, ventricular tachycardia, elevation of liver transaminases, headache, gastrointestinal disorders) and five on diuretic therapy experienced serious side effects (skin rash, palpitation, atrial fibrillation, elevation of liver transaminases, manic episode). One patient died while on diuretic therapy. Only headache and skin rash were considered to be related to the therapy (ibopamine and diuretic therapy, respectively). Our trial suggests that ibopamine can be safely and effectively used as an alternative for diuretics for up to 3 months in patients with mild CHF.