Marc G. Bogaert

Systematic review of clinical efficacy of topical treatments for head lice.

Abstract Objectives: To collect and evaluate all trials on clinical efficacy of topical treatments for head lice. Design: Systematic review of randomised trials identified from following data sources: Medline, International Pharmaceutical Abstracts, Science Citation Index, letters to key authors and companies, and hand search of journals. Setting: Trials in schools or communities. Subjects: Patients infested with lice. Main outcome measure: Cure rate (absence of live lice and viable nits) on day 14 after treatment. Results: Total of 28 trials were identified and evaluated according to eight general and 18 lice specific criteria. Of the 14 trials rated as having low to moderate risk of bias, seven were selected as they used the main outcome measure. These seven trials described 21 evaluations of eight different compounds and placebo (all but two evaluations were of single applications). Only permethrin 1% creme rinse showed efficacy in more than two studies with the lower 95% confidence limit of cure rate above 90%. Conclusions: Only for permethrin has sufficient evidence been published to show efficacy. Less expensive treatments such as malathion and carbaryl need more evidence of efficacy. Lindane and the natural pyrethrines are not sufficiently effective to justify their use.

Binding of oxprenolol and propranolol to serum, albumin and α1-acid glycoprotein in man and other species

Species differences in binding of basic drugs have only occasionally been studied and we have therefore measured the binding of the beta-adrenergic blockers oxprenolol and propranolol in (1) serum of healthy humans, dogs, rats and rabbits and of rabbits with experimental arthritis, (2) a solution of albumin of these species and (3) a solution of human alpha 1-AGP. In humans, dogs, rats and arthritic rabbits, binding of oxprenolol and propranolol was much higher in serum than in albumin solution; in healthy rabbits serum binding was very low and not different from albumin binding. For both drugs, concentration-dependency was seen in serum of dogs, humans and rats and of arthritic rabbits; a similar concentration-dependency was found for human alpha 1-AGP solution, but not for human albumin and for serum of healthy rabbits. Tris (2-butoxyethyl)-phosphate (TBEP), a known displacer of drugs from alpha 1-AGP in humans, decreased binding in serum of all species except the rabbit. For both beta-blockers, species differences in capacity constants were found; species differences in affinity constants were present only for propranolol. These results suggest that in humans, dog and rat, but much less in rabbits, oxprenolol and propranolol bind mainly to alpha 1-AGP and that binding to alpha 1-AGP is more important for oxprenolol than for propranolol.

Determination of nifedipine in human plasma by capillary gas chromatography with nitrogen detection

A gas chromatographic method for the determination of nifedipine in human plasma is presented. Nifedipine was extracted from plasma at basic pH with toluene, and nitrendipine was used as the internal standard. Chromatography was performed on a cross-linked methylsilicone fused-silica column by on-column injection and with a nitrogen-phosphorus ionization detector. The minimal detectable concentration was approximately equal to 0.5 ng/ml of plasma. The standard curve was linear in the range evaluated, 2-300 ng/ml plasma. The within-analysis coefficient of variation was 3.9-10.4%, and the day-to-day coefficient of variation was 3.8%. A peak with the same retention time as the nitropyridine derivative of nifedipine was detected in the plasma of patients who had taken 10 mg nifedipine orally.

Gastric relaxation and vomiting by apomorphine, morphine and fentanyl in the conscious dog

Apomorphine (0.03 mg . kg-1 s.c.) and morphine (0.5 mg . kg-1 s.c.) produced gastric relaxation and vomiting in the conscious dog. Domperidone (0.1-1 mg . kg-1 i.v.), haloperidol (0.1 mg . kg-1 i.v.) and pimozide (0.025 mg . kg-1 i.v.) selectively blocked the gastric relaxation as well as the vomiting caused by apomorphine. Naloxone (0.07 mg . kg-1 i.v.) selectively blocked the gastric relaxation and the vomiting caused by morphine; after naloxone, morphine produced a delayed gastric relaxation in 2 experiments out of 7. These results suggest that for gastric relaxation as well as for vomiting, apomorphine and morphine act on different receptors. Fentanyl elicited marked gastric relaxation, blocked by naloxone, but did not elicit vomiting. After fentanyl, morphine and apomorphine no longer produced gastric relaxation and vomiting. This observation shows that the known blocking effect of fentanyl at the vomiting center does not affect its gastric relaxing effect.

Pharmaceutical policy regarding generic drugs in Belgium

Pressure to control pharmaceutical expenditure and price competition among pharmaceutical companies are fuelling the development of generic drug markets in EU countries. However, in Belgium, the market for generic drugs is underdeveloped compared with other countries. To promote the use of generic drugs, the government introduced a reference pricing (RP) scheme in 2001. The aim of this paper is to discuss Belgian pharmaceutical policy regarding generic drugs and to analyse how the Belgian drug market has evolved following initiation of the RP scheme.The market share held by generic drugs increased following implementation of the RP scheme. Focusing on volume, average market share (by semester) for generic drugs amounted to 2.05% of the total pharmaceutical market from January 1998 to June 2001, compared with 6.11% from July 2001 to December 2003. As new generic drugs are introduced, their market share tends to increase in the first couple of months, after which it levels off. Faced with increasing generic competition, some manufacturers have launched new variants of their original drug, thereby effectively extending the period of patent protection. Strategies consisting of price reductions in return for the abolition of prescribing conditions and the launch of new dosages or formulations appear to have been successful in maintaining the market share of original drugs. Nevertheless, the introduction of the RP scheme was associated with savings amounting to 1.8% of pharmaceutical expenditure by the third-party payer in 2001 and 2.1% in 2002.The findings of this paper indicate that the RP scheme has stimulated the Belgian generic drug market. However, existing policy has largely failed to take into account the role that physicians and pharmacists can play in stimulating generic drug use. Therefore, further development of the Belgian generic drug market seems to hinge on the creation of appropriate incentives for physicians to prescribe, and for pharmacists to dispense, generic drugs. With respect to incentives to advance generic drug use, EU countries have experimented with various forms of budget constraints for physicians, generic substitution by pharmacists and RP schemes, although more evidence is needed of their impact on consumption and prices of generic drugs, pharmaceutical expenditure and health outcomes.

Clinical pharmacokinetics of nitrates

SummaryThe pharmacokinetics of organic nitrates are discussed with emphasis on the possible clinical relevance. For glyceryl trinitrate, the measurement of plasma concentrations is very difficult. Its pharmacokinetics are unusual, with a very rapid disappearance from plasma, and large intraindividual and interindividual variations. After oral administration, there seems to be a very extensive first-pass hepatic extraction and the plasma concentrations are often below the detection limit; after sublingual administration, glyceryl trinitrate appears in plasma. With transdermal glyceryl trinitrate controlled-release systems, plasma concentrations of glyceryl trinitrate can be maintained over 24 hours, although with fluctuations and important intraindividual and interindividual variability. After administration of glyceryl trinitrate via different routes, glyceryl dinitrates and mononitrates are present in plasma. The pharmacokinetics of isosorbide dinitrate are somewhat easier to understand. The substance disappears less rapidly from the plasma than does glyceryl trinitrate. After oral administration, there is also a hepatic first-pass extraction; the plasma concentrations can be prolonged by administering slow-release products. Sublingual administration leads to higher plasma concentrations than oral administration. Isosorbide dinitrate is metabolized in the organism to isosorbide 5-mononitrate and isosorbide 2-mononitrate, which both have vasodilator activity: after administration of isosorbide dinitrate, the mononitrates, and mainly the 5-mononitrate, reach very high concentrations in plasma. Isosorbide 5-mononitrate has been studied in its own right as an antianginal agent: it is completely absorbed after oral administration; it has a half-life of around 4 hours, and oral standard and controlled-release formulations have been extensively studied. For several reasons, including attenuation of the effects with time and the appearance of active metabolites, the relationship between the plasma concentrations of nitrates and their therapeutic effects is very complex. Knowledge of the pharmacokinetics of these substances is only of limited interest.

Impact of patient package inserts on patients' satisfaction, adverse drug reactions and risk perception: The case of nsaids for posttraumatic pain relief

Objective: The main objective of this study was to measure the impact of the patient package insert (PPI) of a nonsteroidal anti-inflammatory drug (NSAID) on patient satisfaction with medication information, on medication risk perception and on the reporting of adverse drug reactions (ADRs), as compared with the impact of the traditional (physician-oriented) insert. Design: A randomized clinical trial was conducted, with random allocation of the PPI and the traditional insert. The physicians were blinded for the experimental condition. A follow-up visit was scheduled after one week. Setting: 42 volunteering general practitioners (GPs) from the Dutch-speaking part of Belgium selected the patients. Patients: Every GP had to select, during a period of approximately 6 months between March 1989 and February 1990, a consecutive sample of patients with acute injuries of the locomotor system, for whom he would, for symptomatic therapy, prescribe an NSAID in his routine practice. A total of 366 patients was selected, 317 of whom completed the study. Intervention: All patients selected received a package of the NSAID pirprofen (30 capsules of 200 mg) from their GP. This package contained (at random) a PPI or a traditional insert. Measurements and main results: the GPs had to complete case records (clinical details, ADRs reported spontaneously). Patients received a self-administered questionnaire (identification, readership, satisfaction, risk perception, influences on decision taking and health problems that could be ADRs) at the second visit. Satisfaction, risk perception and influences on decision taking were measured on unlabeled semantic differential 7-point scales. On the whole, package inserts were read by 71% of the patients (N = 317). PPIs were not read more frequently than traditional inserts. PPIs were found to be more understandable (P < 0.001), but overall satisfaction with the inserts was high for both types. A less favorable assessment of the benefits as compared with the risks of the medication was found among patients who read the insert and within this group among patients who received the PPI. Patients who read the insert were more likely to report health problems that could be ADRs, both spontaneously (P < 0.001) and on a checklist (P = 0.025). They were also more likely to attribute health problems to the medication (P = 0.005) and to stop taking the medication because of ADRs. Patients who received a PPI were more likely to report possible ADRs as well, but this was statistically significant (P = 0.034) for spontaneous reporting only. Conclusions: The patients were very satisfied with both the traditional package insert and the PPI. Clear, understandable risk information in package inserts in the setting of an optional symptomatic treatment of an acute self-limiting disease, has some impact on how patients perceive, appraise and manage medication risks. Therefore, the PPI is an important instrument in adequate communication concerning the benefits and risks of drugs and should be drafted and handled in an appropriate way.

Pharmacological characterization of the postjunctional β-adrenoceptors in the rat gastric fundus

In order to characterize the postjunctional beta-adrenoceptors in the rat gastric fundus, we studied the influence of beta-agonists and beta-antagonists on methacholine-contracted fundus strips. The mixed beta-agonist isopropylnoradrenaline and the beta 2-selective agonist fenoterol had a concentration-dependent relaxing effect and at higher concentrations completely inhibited the methacholine-induced tone. The reputedly beta 1-selective agonist prenalterol only produced about 50% inhibition and another reputedly beta 1-selective agonist, tazolol, had almost no relaxing effect. The beta-antagonists propranolol (beta 1 + beta 2), practolol (beta 1), H35/25 (beta 2) and ICI 118,551 (beta 2) all shifted the concentration-response curves for isopropylnoradrenaline and fenoterol in a parallel way to the right, but the slope of the Schild plot was not significantly different from 1 only for the antagonism of isopropylnoradrenaline by H35/25. The relaxing effect of prenalterol was only clearly antagonized by ICI 118,551. The results suggest that postjunctional beta 1- and beta 2-adrenoceptors are present in the rat gastric fundus.

Radioimmunoassay of digoxin in renal failure: A comparison of different commercial kits

Six commercially available kits for radioimmunoassay of digoxin were compared. When serum from patients with chronic renal failure on maintenance digoxin therapy was analysed, important discrepancies in the results obtained with the 6 kits were found in some of these patients. However, recovery of digoxin added to serum of a healthy volunteer, was within acceptable limits and comparable for the 6 kits. In patients with renal failure not taking digoxin but several other medications, digoxin estimations gave results close to zero. The affinity of the antibodies for some metabolites of digoxin was also assessed: important differences between the kits were found.

Relation between coronary-prone behavior pattern, excretion of urinary catecholamines, heart rate, and heart rhythm.

Abstract In a group of middle-aged men exhibiting the type A or B behavior pattern described by Rosenman and Friedman, the excretion of urinary catecholamines and their metabolites has been studied during a working-day period. Simultaneously, heart rate and heart rhythm were analyzed using continuous ECG recordings. No significant differences were observed between subjects classified as type A and those classified as type B, neither in the excretion of catecholamines, in their heart rate profile, nor in the prevalence of arrhythmias. These observations are discussed and compared with data from the literature.