[An evaluation of the therapeutic activity and tolerance of ST-679 in patients with osteoarthritis at different sites. A controlled double-blind study vs tolmetin]. / Valutazione dell'attività terapeutica e della tollerabilità di ST-679 in pazienti affetti da osteoartrite a diversa localizzazione. Studio doppio cieco controllato vs tolmetina.

A multicentered study was carried out, under double-blind conditions, on 160 elderly patients afflicted with differently localized symptomatic osteoarthritis, for the purpose of evaluating the therapeutical efficacy and tolerability of ST-679 (per-os at a dose of 1200 mg pro die in 80 patients) and to compare them with those of tolmetin (per os at a dose of 1200 mg pro die in 80 patients). It was demonstrated that ST-679 was significantly active on all of the clinical parameters of the illness already recorded after a month of treatment. ST-679 was always excellently tolerated as shown by the scarce incidence of adverse reactions. Results of laboratory tests, of tests for hidden blood in the feces and of a gastroduodenoscopy confirmed the excellent biological and gastric tolerability of ST-679. ST-679 demonstrated, moreover, a significantly better tolerability with respect to tolmetin.

Variation in levels of glycaemia and insulin after infusion of glucose solutions with or without added L-carnitine.

The effect of L-carnitine on glucose and insulin plasma levels was evaluated in 47 healthy volunteers who were administered a 10% glucose solution infusion over 3 h. The experiment was carried out following a cross-over procedure: each patient received two 750 cc 10% glucose solution infusions, a week apart; to one of these infusions 6 g L-carnitine had been added. The glucose infusion significantly increased the plasma glucose concentration of both groups, however, analysis of variance demonstrated that the increase in Group B was inferior (p < 0.01). Insulin plasma levels increased rapidly after the beginning of the glucose infusion in both groups. From T90 to T180, when the maximum hypoglycaemic effect of L-carnitine was observed, this increase was lower in Group B than in Group A. The authors conclude that L-carnitine is capable of reducing the increase in plasma glucose concentration induced by a glucose solution infusion in healthy subjects. This effect does not seem to be related to an insulin-dependent mechanism.

Steady-state pharmacokinetics of idebenone in patients with moderate renal impairment.

Idebenone (45 mg twice daily) was administered to 7 patients with moderate renal impairment (creatinine clearance 21-40 ml/min) for 10 days. Standard pharmacokinetic parameters were computed on day 1 (single administration) and on day 10. On day 1 the mean of the maximum plasma concentration values (C(max)) was 364 ng/ml (standard deviation (S.D.) 100); time to C(max) (t(max)) was in the range of 1-2 h for 6 patients and 12 h for the remaining patient: the mean was 3 h (S.D. 3.99); the mean area under the plasma concentration vs. time curve (AUC) was 3005 ng h/ml (S.D. 1152). On day 10 the mean C(max) was 531 ng/ml (S.D. 355.3), the mean t(max) was 0.07 h (S.D. 0.19), the mean AUC was 3167 ng/ml (S.D. 2944) and the mean elimination half-life (t(1/2)) was 4.9 h (S.D. 1.1). Idebenone metabolites (QS-4, QS-6 and QS-10) showed a kinetic profile similar to the parent compound, with pharmacokinetic parameters comparable to idebenone for QS-4 and lower than idebenone for QS-6 and QS-10. Idebenone was metabolized and easily excreted and no accumulation was observed for the compound and its metabolites. No significant modification of the biohumoral indexes and vital signs and no adverse reactions were observed.

Evaluation of the clinical efficacy of idebenone in patients affected by chronic cerebrovascular disorders.

This study evaluated the efficacy and tolerability of idebenone, a new neuroactive drug, in 33 patients aged from 50 to 80 years. They were affected by chronic cerebrovascular disease (CCVD) and their last cerebrovascular accident had taken place at least 3 months prior to enrollment. All these subjects presented a score within the range of the following psychometric scales: Hamilton Scale for Depression <24; Hachinski Dementia Score >/=18 and < 25; Mini Mental State >/=16 and

The therapeutic effect of L-carnitine in patients with exercise-induced stable angina: a controlled study.

An investigation on the therapeutic effect of L-carnitine was performed at three different centres and included two hundred patients, 40 to 65 years of age, with exercise-induced stable angina. In one hundred randomly selected patients the drug was administered orally in daily doses of 2 g in addition to the already instituted therapy, and the effect studied over a 6-month period. Compared with the control group, these patients showed a significant reduction in the number of premature ventricular contractions (PVC) at rest, as well as an increased tolerance during ergometric cycle exercise as demonstrated by an increased maximal cardiac frequency, increased maximal systolic arterial blood pressure and therefore also increased double cardiac product and reduced ST-segment depression during maximal effort. This was accompanied by improvement in cardiac function and resultant performance, as shown by an increase in the number of patients belonging to class I of the NYHA classification and a reduction in the consumption of cardioactive drugs. Laboratory analysis showed an improvement in plasma lipid levels. The authors conclude, after having discussed the particular metabolic mechanisms, that L-carnitine undoubtedly represents an interesting therapeutic drug for patients with exercise-induced stable angina.