[Evaluation of pindolol absorption in malabsorption syndromes]. / Evaluation de l'absorption du pindolol dans les syndromes de malabsorption.

Reports on drug absorption in intestinal diseases are scarce. To investigate pindolol absorption, a drug particularly well absorbed and with low hepatic extraction, plasma concentrations and 54-h urinary excretion (after both oral and intravenous dose) were studied in 6 healthy volunteers and 13 patients with intestinal malabsorption (coeliac disease 5 cases, short bowel syndrome 8 cases) after an overnight fasting. Pindolol plasma concentrations were almost identical after a single intravenous dose in both patients and controls. Again mean blood levels after an unique oral dose were not significantly different between the two groups. However, absorption was slow and/or delayed in eight out of thirteen patients and overall absorption was decreased in two of them. These abnormalities might be related to the diseased intestine, since plasma concentrations and urinary excretion following intravenous administration were quite similar to those observed in volunteers. Nevertheless, results were not related to the extent of the intestinal disease nor the degree of impairment of small intestinal function.

Study of prophylaxis by didecyl dimethyl ammonium chloride against herpes simplex virus infection in nude mice.

Primary or recurrent viral infections, especially by herpetoviridae, with viraemias--after organ transplants, for example--are a serious medical problem which can affect the prognosis for survival. An experimental protocol for the prevention of infection by a herpes simplex virus type 1 was applied to Nude mice infected via inhalation. It suggests the possibility of appreciably limiting viral infection by the parenteral use of didecyl dimethyl ammonium chloride. The results are encouraging and could lead to further experimental studies to prove the efficiency of this molecule whose level of toxicity can be disassociated from its antiviral action to limit the infections by other enveloped viruses.

Cardiovascular beta-adrenergic blocking effects of bornaprolol in humans: relation to dose and plasma concentration.

The cardiovascular beta-blocking effects of bornaprolol were studied in healthy male volunteers after four single oral doses. The inhibition of isoproterenol-induced tachycardia was monitored for 72 h in six subjects, and the inhibition of exercise-induced tachycardia and rise of systolic blood pressure were monitored for 167 h in six other subjects. Plasma drug concentrations were determined by gas chromatography. Bornaprolol significantly reduced the resting heart rate, isoproterenol- and exercise-induced tachycardia, and effort hypertension. The peak effect was obtained within 1-2 h of drug administration and was correlated with dose. The effect on the isoproterenol test remained significant for 6 h after administration of 40 mg bornaprolol, and 72 h after 80, 120, and 240 mg. The effect of bornaprolol on the exercise test in comparison with placebo was significant during 23 h (120 and 240 mg) and 47 h (480 and 960 mg). A positive relationship was found for both tests between the maximum effect and the doses administered. A correlation was also found for each group of subjects between the time course of the plasma drug concentration and the effects of each bornaprolol dose on isoproterenol- and exercise-induced tachycardia. The beta-blocking effects in individual subjects, however, often continued long after the disappearance of detectable plasma drug concentrations.

Estimation of the absolute oral bioavailability of pindolol by two analytical methods.

The absolute oral bioavailability of pindolol has been estimated by two analytical methods, fluorimetry and GLC-ECD. The study was carried out in six healthy subjects who received either i.v. or oral pindolol in random order. The results obtained by both methods were similar and confirm the high bioavailability (about 75%) of pindolol. The present findings are compared with previous publications and emphasize the importance of undertaking bioavailability studies in the same subjects.

Pharmacokinetic characteristics of bornaprolol in healthy volunteers.

1. Six young male volunteers received five single doses of bornaprolol, i.v. (20 mg) and orally (120, 240, 480, 960 mg) administered at 2-week intervals. Plasma concentrations of bornaprolol and its conjugated metabolite were determined by gas chromatography. 2. After i.v. administration, plasma bornaprolol levels were detectable over 8 h, and mean values were 60 l/h for total clearance (C1), 207 l for volume of distribution (V beta), 2.6 h for elimination half-life (t1/2 beta). After oral administration, plasma bornaprolol levels were detectable over 24-48 h, and mean values of pharmacokinetics parameters were 60 l/h for C1, 1500 l for V beta, 20 h for t1/2 beta. Maximum plasma concentrations and area under the plasma concentration-time curve increased in a non-dose-dependent manner. 3. The glucuronide conjugate appeared in the blood within 5-10 min and its plasma level greatly exceeded bornaprolol concentrations. The mean value of the ratio of the metabolite AUC/parent product AUC was 14 after i.v. administration and 13-21 following oral administration, depending on dose. The AUC for the metabolite did not increase proportionally with oral doses. 4. Bornaprolol is principally eliminated after metabolism. This process did not increase with increasing oral doses and bioavailability seemed to decrease inversely with oral dose.

Study of the bioavailability of pindolol in malabsorption syndromes.

Pindolol kinetics and bioavailability were studied after a single dose (oral 5 mg; intravenous 3 mg) in nine patients with malabsorption (two with villous atrophies, seven with short bowel syndromes) and in six healthy volunteers. After oral administration no significant differences were observed in bioavailability (59.4 +/- 6.2% in patients vs 79.5 +/- 8.6% in controls) and for most plasma and urinary pharmacokinetic parameters between the experimental and control groups as a whole. However, detailed analysis revealed decreased absorption for pindolol in two out of nine patients. After i.v. administration, apparent distribution volume was smaller (V: 2.10 +/- 0.25 l kg-1 vs 3.05 +/- 0.31 l kg-1) and global elimination constant was larger (ke: 1.43 +/- 0.46 h-1 vs 0.56 +/- 0.10 h-1), in patients with malabsorption than in controls (P less than 0.05). The smaller weight of patients and pharmacokinetic modifications due to the pathology could account for this.