Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin

A subgroup of 16 out of 30 endogenous depressive inpatients (cf. part I), treated for 3 weeks with 150 mg amitriptyline (AT) daily, participated in a pharmacogenetic study: all were phenotyped with debrisoquine and 3 of them with mephenytoin. Four patients were found to be poor metabolizers (PMs) of debrisoquine and one of mephenytoin. Plasma levels of AT + NT (nortriptyline) were highest in the PMs of debrisoquine, but the ratio of hydroxylated metabolites to the parent compounds appeared to be lower in these subjects. From these data, it is speculated that, in the PM of mephenytoin, the demethylation of AT is impaired. In 12 patients, free plasma 10-hydroxy-AT (ATOH) and 10-hydroxy-NT (NTOH) were found to be bound to a similar extent to plasma proteins, but not so firmly as their parent compounds, by a factor of 6 and 4 respectively. While mean total plasma ATOH reached only 15% of the value of AT, total plasma NTOH was as high as NT. ATOH correlated significantly with its parent compound, but NTOH did not correlate with NT. No drug plasma levels/clinical relationship was found in this small group of patients, even when the hydroxylated metabolites were taken into account. Both poor and extensive metabolizers of debrisoquine responded to treatment. The debrisoquine-test appears to be a useful clinical tool for detecting in patients a genetic deficiency in the hydroxylation of AT-type drugs.     

Oesophageal ulcerations and plasma levels of different alprenolol salts: potential implications for the clinic

The ulcerogenic effect of five different salts of alprenolol were tested against placebo in a porcine oesophageal test model. The salts with high water solubility, such as the hydrochloride and the fumarate, gave rise to the highest plasma concentrations of alprenolol and evoked serious oesophageal lesions, while the salts with low solubility-the benzoate, maleate and sebacate-had no irritative effect on the oesophagus. The plasma levels of alprenolol were much higher following administration of alprenolol hydrochloride in the oesophagus than after an identical intraduodenal dose of the same salt possibly because of the avoidance of the first-pass degradation during oesophageal absorption.     

Hand hygiene and glove use behavior in an Italian hospital.

In an Italian hospital, we observed that hand hygiene was performed in 638 (19.6%) of 3,253 opportunities, whereas gloves were worn in 538 (44.2%) 1,218 of opportunities. We observed an inverse correlation between the intensity of care and the rate of hand hygiene compliance (R2=0.057; P<.001), but no such association was observed for the rate of glove use compliance (R2=0.014; P=.078). Rates of compliance with hand hygiene and glove use recommendations follow different behavioral patterns.     

Enzyme immunoassay for the determination of IgE antibodies specific to grass pollen allergens using monoclonal antibodies of the BL-IgE series. 2. Performance and results of a collaborative study to evaluate the test system

This paper describes performance and results of a collaborative study in which the solid-phase enzyme immunoassay was tested in order to determine specific IgE under practical conditions. All titres of specific IgE can be differentiated in a reproducible way with high significance.