A. Loffreda

Serum digoxin levels after concomitant ticarcillin and clavulanic acid administration.

Summary Recently it has been recognized that steady-state serum digoxin concentrations may increase or fall to ineffective levels when the glycoside is administered together with several antibiotics. Our study was designed to assess if serum digoxin levels may be modified by the concomitant use of a ticarcillin and clavulanic acid. The study was carried out in 15 hospitalized patients suffering from exacerbation of their chronic bronchitis without liver disease and renal failure. Serum digoxin levels were not significantly modified by the concomitant use of a ticarcillin and clavulanic acid, although peak digoxin serum concentrations were slightly lower. However, the average time to achieve the maximum concentration and area under the curve over 24 h did not change.

Vasomotor reactivity and catecholamine, arginine vasopressin plasma levels during ageing and development in rats

Vascular reactivity, heart rate responses to vasoconstrictor and/or vasodilatator agents and catecholamine and arginine vasopressin turnover were studied in normotensive Wistar Kyoto (WKY), spontaneously hypertensive (SHR), normolipemic Brown Norway (BN) and spontaneously hyperlipemic Yoshida (YOS) anaesthetized rats at 2, 6 and 18 months of age. In this study, we investigated whether ageing and development could affect cardiovascular reactivity to vasoactive substances and catecholamine and arginine vasopressin turnover. No significant changes in the pressor responses to noradrenaline and to carotid sinus baroreceptor stimulation were observed nor were there significant alterations in reflex tachycardia and bradycardia. Arginine vasopressin plasma levels also did not change with ageing and development. On the other hand, the hypotensive responses to isoprenaline decreased in old rats, acetylcholine relaxation effect increased with ageing and development in some rat strains (BN and YOS) and catecholamine plasma levels increased with ageing and development. Our results indicate that during ageing and development, vascular responsiveness to vasoconstrictor and/or vasodilatator agents, as well as amine turnover, may increase, decrease or not change at all depending on the neurotransmission system studied, and on the experimental model and/or animal tested.

Use of naltrexone for the treatment of opiate addiction in Campania, Italy: the role of family

In Italy, naltrexone for the treatment of opioid dependence is frequently administered to opiate‐dependent patients sent for treatment via special treatment facilities, the Public Services for Treatment of Drug Addition (SERT). In the region Campania, prescription data showed that the use of naltrexone outside SERT is higher compared to the other regions of Italy. This study was carried out in order to identify factors that influence the higher utilization of naltrexone outside SERT in Campania. Three‐hundred and fifty patients followed by 13 SERTs have been evaluated. Twenty per cent of patients withdrew from the trial in the very first months. At the beginning of the study, 63% of the patients received naltrexone at SERT, while 37% were treated at home with the support of their families. Later during treatment, the majority of patients were treated at home. Families showed a high degree of participation and cooperation in the rehabilitation of patients (75%). These data suggest that the support of families was especially important for motivation of retention treatment and integration with psychosocial programmes. Naltrexone treatment can be continued at home after a short period of treatment from the public service if families intensively participate in the therapeutic programme.

BIOEQUIVALENCE ASSESSMENT OF TWO DIFFERENT TABLET FORMULATIONS OF DILTIAZEM AFTER SINGLE AND REPEATED DOSES IN HEALTHY SUBJECTS

The study was performed on 14 healthy volunteers in order to compare the pharmacokinetics and hence assess the bioequivalence of two different tablet formulations of diltiazem administered orally. The study was carried out after single doses (60 mg) and repeated doses (60 mg three times a day for six days and 60 mg on the seventh day) according to a randomised, cross-over, open design. The pharmacokinetic parameters AUC0-infinity (ng h/ml), Tmax(h) and Cmax (ng/ml) were calculated for the two formulations after a single dose, while AUCt1-t2 (= AUC for a repetitive dose interval or dosing cycle, ng h/ml) and PTF (peak trough fluctuation) were calculated after repeated doses. The bioequivalence assessment was the shortest 90% confidence interval for the ratio (difference) of expected medians in the respective bioequivalence range (0.80-1.20). The results of this study show that, after either a single dose or repeated doses of test or reference formulations of diltiazem, the pharmacokinetics of the two formulations are similar. The ratios of AUC on day 1 (for single-dose treatment) and on day 7 (for repeated-dose treatment), and the corresponding 90% confidence intervals demonstrate bioequivalence between the two formulations of diltiazem within the accepted range of 0.80-1.20 (80-120%).