Penetration of enrofloxacin into the nasal secretions and relationship between nasal secretions and plasma enrofloxacin concentrations after intramuscular administration in healthy pigs.

The pharmacokinetic behaviour of enrofloxacin (ENRO) in plasma and nasal secretions of healthy pigs was investigated, after a single-dose intramuscular administration of 2.5 mg/kg body weight of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. Concentrations of ENRO and its active metabolite ciprofloxacin (CIPRO) were determined in plasma and nasal secretions by high-performance liquid chromatography (HPLC). CIPRO was not detected probably because we investigated young weaned pigs. The data collected in 12 pigs for ENRO were subjected to noncompartmental analysis. In plasma, the maximum concentration of drug (C(max)), the time at which this maximum concentration of drug (T(max)) was reached, the elimination half-life (t(1/2)(beta)) and the area under the concentration vs. time curve (AUC) were, respectively, 694.7 ng/mL, 1.0 h, 9.3 h and 8903.2 ngxh/mL. In nasal secretions, C(max), T(max), t(1/2)(beta) and AUC were, respectively, 871.4 ng/mL, 2.0 h, 12.5 h and 11 198.5 ngxh/mL. In a second experiment conducted in 10 piglets, the relationship between concentrations of ENRO measured in the plasma and the nasal secretions has been determined following single-dose intramuscular administration of 2.5, 10 or 20 mg/kg body weight of the drug. It has been demonstrated that, among several variables, i.e., (1) the dose administered, (2) the time between intramuscular injection and blood sampling, (3) the age, (4) the sex, (5) the animal body weight and (6) the plasma concentration of the drug, only the latter influenced significantly the ENRO concentration in nasal secretions. Practically, using a generalized linear mixed model, ENRO concentrations in the nasal secretions (microg/mL) can be predicted taking into account the ENRO concentrations in plasma (microg/mL), according to the following equation:

[Generic medications and prescription by non-proprietary name]. / Le point sur les médicaments génériques et sur la prescription sous dénomination commune.

Complementarily to a previous publication, this paper tries to answer a few commonly asked questions about--generic medications: pharmaceutical quality, bioequivalence and therapeutic equivalence, substitution, etc. A summary of recent regulations about reference price and prescription by non-proprietary name, aiming at the promotion of generic medication prescription is also presented.

[Generic drugs]. / Les médicaments génériques.

Various incentives will progressively increase the part of generic drugs on the Belgian market place and will more and more confront the prescriber with the problem of substitution. The equivalence between generic and brand name products and the fear, justified or not, at efficacy or patient safety levels in case of substitution are discussed on the basis of biopharmacy and pharmacokinetic concepts in connection with modalities generally adopted when requesting marketing authorisation. Considering the extent of their utilisation at international level and the low frequency of clinically significant problems linked to bioequivalency, limited to a small number of substances, prescribers should be soon released from their apprehensions on the quality of generic drugs. On another hand, they must be stimulated to be vigilant when they substitute a drug by any other one, especially in the cases of drugs, classes of drugs, or pharmaceutical forms considered as critical and when occurring to patients whose disease or physiological status are able to amplify bioequivalence problems.

[Pharmaco-economic aspects of the treatment of hypertension]. / Aspects pharmaco-économiques du traitement de l'hypertension.

Hypertension affects a large proportion of the adult population. Subsequently any change in treatment strategy may have a drastic impact on health expenditure especially when one decides to decrease the limits of arterial pressure beyond which a treatment is started. Results of pharmaco-economic studies are often controversial because they are mainly based on an evaluation of short-term absolute risks, maybe underestimating the benefit of a treatment in younger population with mild to moderate hypertension. All groups of antihypertensive drugs are able to reduce the blood pressure and most of them can induce a light improvement of patient quality of life. Diuretics and beta-blockers have a lower cost/effectiveness ratio. ACE inhibitors and calcium antagonists may be preferred when other drugs are badly tolerated or when some other morbidities affect the patient.

[Pharmaco-economic aspects of antibiotic therapy in hospitals]. / Aspects pharmaco-économiques de l'antibiothérapie à l'hôpital.

Amongst medications used in hospitals, antibiotics represent the most expensive therapeutic group; their use is constantly growing. Beyond acquisition costs, antibiotherapy costs must be approached at a broader level, including costs of preparation, administration, efficacy or inefficacy, monitoring, side effects treatment, and long-term costs resulting bacteria resistance. An attempt to cost containment in antibiotherapy can only result from a global, multidisciplinary strategy, with at all levels, as main objectives, the improvement of the quality and effectiveness of treatment adequate relevance of drug selection and therapy assessment.

[The pharmaco-economics of the treatment of arterial hypertension: data and controversies]. / Pharmaco-economie du traitement de l'hypertension artérielle: données et controverses.

The cost benefit ratio of antihypertensive therapy motivated many researches and discussions these last years. The treatment of this very frequent and chronic abnormality is of importance in this time of shortage of money available for health care. Its cost benefit ratio appears to decrease with age and the severity of hypertension: but these calculations rest on several hypotheses, that need scientific demonstrations by prospective data retrieval.

Drug utilization review of oral forms of benzodiazepines in a Belgian 635-bed teaching hospital.

A retrospective study based on 4,307 drug patient records was designed to establish a chart of the consumption of benzodiazepines administered orally in a 635-bed teaching hospital, and to determine the influence of patient-related parameters (age, sex) and hospital-related parameters (type of services, prescription habits, etc.) on benzodiazepine utilization. Another objective was to evaluate to which extent benzodiazepine consumption can be induced by hospitalization. A minor but statistically significant difference (p < 0.05) was observed between the proportion of male (42.7%) and female (46.5%) users. Besides, when evaluating the consumption in number of defined daily doses per 100 beddays, there was little difference between the consumption of male (51.2 defined daily doses per 100 beddays) and female (52.8 defined daily doses per 100 beddays) patients. A significant influence of age was also observed with an increase of benzodiazepine use for patients aged from 15-20 to 40-45, followed by a progressive decrease for higher ages. With hypnotics, no peak of consumption related to age was observed but an increase of consumption from age 15-20 to 30-35. For higher ages the consumption of hypnotics was nearly stable or rising slowly. High variations in benzodiazepine utilization were recorded between hospital wards (median: 50.77 defined daily doses per 100 beddays, range 0.23-263.9). Finally, it was found that 6.8% of patients with a benzodiazepine treatment initiated during hospitalization may be considered as potential benzodiazepine consumers after discharge.

Effect of indomethacin on the metabolic and hormonal response to a standardized breakfast in normal subjects.

We have investigated the influence of a single oral administration of indomethacin on blood glucose, plasma free fatty acids (FFA), alpha-amino-nitrogen, insulin and glucagon concentrations in young healthy subjects. Two groups of 6 subjects were studied, the first received a standardized 500 kcal mixed meal without any previous drug administration (controls) whereas the second group received 50 mg indomethacin 2 h before ingesting an identical meal. Plasma indomethacin concentration reached its maximum (2.36 +/- 0.36 micro g/ml) 15 min after administration and declined to 0.45 +/- 0.04 micro g/ml after 2 h. Indomethacin ingestion was followed by a significant increase in blood glucose and plasma FFA reaching their maximum value at 45 min and returning to basal levels at 120 min. No simultaneous changes in plasma alpha-amino-nitrogen, insulin or glucagon levels were detected during this period. The meal was followed by a rise in blood glucose and plasma insulin as well as by a decrease in plasma FFA concentration. No significant differences were detected between the controls and the subjects receiving indomethacin. In controls, the meal was followed by a rise in plasma alpha-amino-nitrogen and a modest although significant increase in glucagon levels. In indomethacin-treated subjects, the increment of alpha-amino-nitrogen was less marked and the increase in plasma glucagon was not observed. Thus, indomethacin by itself can exert several metabolic effects; however, it does not deteriorate the blood glucose or insulin profile after a regular meal. The present work is the first to demonstrate that an inhibitor of prostaglandin synthesis inhibits the plasma glucagon rise occurring after a physiological stimulus such as a normal meal. On the basis of previous in vitro experiments, we suggest that this effect results from an inhibition of glucagon secretion by the PG synthesis inhibitor.