M G Bogaert

Ghent University, Gand, Flanders, Belgium

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Publications (210)553.28 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A study was carried out in 14 patients suffering from chronic obstructive lung disease with partially reversible airway obstruction to evaluate a new, sustained-release theophylline preparation (‘Theolair SR”) at two dosages, 350 mg twice daily and 500 mg twice daily at 12-hourly intervals. Serial measurements were made of plasma theophylline concentrations and lung function after a multiple-dose regimen leading to steady-state with both dosages. The results showed that there was a marked improvement in lung function measurements and subjectively there was little difference between the two regimens. Plasma theophylline concentrations showed little variation when steady state was reached. Side-effects, mainly nausea and epigastric discomfort, were mild and only reported by half of the patients.
    Current Medical Research and Opinion 08/2008; 6(s6):132-141. DOI:10.1185/03007997909115920 · 2.65 Impact Factor
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    ABSTRACT: Intermittent claudication (IC) is pain that develops in a limb (mostly calves and thighs) during exercise and is relieved with rest. It is caused by insufficient blood flow due to peripheral arterial occlusive disease. Treatment should contain all measures of secondary prevention of cardiovascular diseases. Regular exercise and smoking cessation is the most effective therapy to improve the symptoms of claudication. Drug treatments include vasoactive agents to improve blood flow (such as vasodilators and other hemorheologic agents that reduce blood viscosity), anticoagulants, antiplatelet agents and lipid-lowering agents. Only a minority of patients undergo angioplasty or vascular surgery. Buflomedil is a vasoactive agent widely used to treat intermittent claudication. The review authors identified eleven trials but could not use nine of them because of the methodologies used and high risk of bias. The two remaining controlled trials randomised a total of 127 participants to receive buflomedil or placebo for at least three months. One of these trials involved 40 participants with diabetes. Taken together, the trials showed moderately positive results for improvements in pain-free walking distance on a treadmill (76.9 m, 95% CI 32.3 to 121.5) and maximum walking distance (112.6 m, 95% 27.7 to 197.5) with buflomedil for 12 weeks, showing a wide variation in benefit between participants. The excluded studies consisted of three small marginally positive studies and one larger negative study. At least another four unpublished studies could not be retrieved and were reported to have inconclusive results. Recent safety concerns have been raised about buflomedil because of lethal and non-lethal neurologic and cardiovascular advents events in cases of accidental and voluntary overdoses. The benefit of buflomedil is small in light of relatively little evidence on efficacy and narrow therapeutic range along with recent safety issues.
    Cochrane database of systematic reviews (Online) 02/2008; 3(1):CD000988. DOI:10.1002/14651858.CD000988.pub3 · 6.03 Impact Factor

  • Praxis 01/2003; 92(01):34-35. DOI:10.1024/0369-8394.92.1.34
  • T L M de Backer · R H Vander Stichele · M G Bogaert ·
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    ABSTRACT: Intermittent claudication is pain, caused by chronic occlusive arterial disease, that develops in a limb during exercise and is relieved with rest. Buflomedil is a vasoactive agent claimed to have beneficial effects on the microcirculation. It is used chiefly to treat peripheral vascular disease and to a lesser extent for cerebrovascular arterial disease. However, its clinical efficacy for intermittent claudication has not yet been critically examined. To evaluate the available evidence on the efficacy of buflomedil for intermittent claudication. We searched Medline, International Pharmaceutical Abstracts (IPA) and the Cochrane Controlled Trials Register. Abbott Laboratories, the distributor of buflomedil, was asked to provide reports of controlled clinical trials. Reference lists of retrieved articles were checked, and enquiries sent to authors of known trials, to identify additional trials. Finally, we conducted a Science Citation Index search. Trial reports had to be double-blinded, randomized, and conformed to our PIO-criteria (Patients, Intervention, Outcome) to be considered for inclusion. Patients were required to have proven intermittent claudication (Fontaine stage II); the intervention was to be oral administration of buflomedil compared to placebo; and outcomes had to include pain-free walking distance (PFWD) and maximum walking distance (MWD) analysed by standardized exercise test. Searches of bibliographic databases yielded three eligible randomized controlled trials (RCTs) and a meta-analysis referring to nine eligible trials. Two of these nine trials had already been identified; two had been published in journals not referenced in traditional bibliographic indexes; and five were unpublished. Despite multiple requests, only one of the five unpublished trials was provided by the author of the meta-analysis, the other four could not be retrieved. Four of the six eligible trials retrieved were subsequently excluded after quality evaluation. Data on walking distances were extracted from the two remaining trials. Differences in incremental gain between active and placebo groups for PFWD and MWD with their confidence intervals were calculated. Both RCTs showed moderate improvements in PFWD for patients on buflomedil. In one trial this improvement (75 m, 95% CI 37-114) was statistically significant, but in the other, with a wholly diabetic population, it was non-significant (81m, 95% CI -9-170) compared to placebo. For both RCTs the gains in MWD were statistically significant, but with wide confidence intervals (81 m, 95% CI 30-131; and 171 m, 95% CI 27-316 respectively). Pooling of the data was not attempted. There is little evidence available to evaluate the efficacy of buflomedil for intermittent claudication. Most available trials are of poor quality and were excluded. The two trials included showed moderately positive results but these are undermined by publication bias since we know of another four unpublished, irretrievable, and inconclusive studies. There is a lack evidence for the efficacy of buflomedil in intermittent claudication.
    Cochrane database of systematic reviews (Online) 02/2001; DOI:10.1002/14651858.CD000988 · 6.03 Impact Factor
  • T L De Backer · R H Vander Stichele · H H Warie · M G Bogaert ·
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    ABSTRACT: To evaluate the role of orally administered vasoactive medication in the management of intermittent claudication. We limited our study to the products on the market in Belgium: cinnarizine, cyclandelate, isoxsuprine, naftidrofuryl, pentoxifylline, xanthinol nicotinate and buflomedil. We conducted a systematic literature search involving Medline, International Pharmaceutical Abstracts, the Cochrane Library, direct contact with marketing companies and key authors, snowballing and Science Citation Index search. We looked for randomised placebo-controlled trials (RCTs) in patients with Fontaine stage II, in which pain-free and/or maximal walking distance were measured using a standardised exercise test. For isoxsuprine and xanthinol nicotinate, no trials conforming to these criteria were found. Thirty-six trials on cinnarizine, cyclandelate, buflomedil, naftidrofuryl and pentoxifylline met our inclusion criteria. After quality assessment, 26 trials were excluded, mainly because of short trial duration (less than 12 weeks), small sample size (less than 30 patients) and/or failure to report details on variability (standard deviation or confidence limits). For cinnarizine and cyclandelate, none of the three selected RCTs was included. For buflomedil, of six published RCTs, two were included after quality assessment, each showing a marginally positive effect of buflomedil versus placebo. For naftidrofuryl, nine RCTs were selected; six were included of which five showed a significant positive result. The likelihood of publication bias and the heterogeneity of the results within and between trials precluded a meta-analysis. For pentoxifylline, of the 18 selected RCTs, only two could be included, both with inconclusive results. A national consensus conference, based on this review, concluded that health resources should be allocated to prevention and rehabilitation of intermittent claudication rather than to reimbursement of these products with doubtful efficacy.
    European Journal of Clinical Pharmacology 07/2000; 56(3):199-206. DOI:10.1007/s002280000114 · 2.97 Impact Factor
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    ABSTRACT: To study, in institutionalized mentally retarded patients, the prevalence of regular laxative use, and to identify its correlates. Twenty-one of the 22 institutions for the mentally retarded in Flanders (Belgium) provided the setting for the study, which included a population of 3712 residents with an IQ of < 50. This was a descriptive cross-sectional study of a random sample of 20 patients per institution, consisting of a structured interview of the personnel responsible for daily care of the selected patients. The study population consisted of 420 mentally retarded patients. Their median age was 29 years (range 2-72 years). Twenty-six percent of patients had an IQ of 35-49, 40% an IQ of 20-34 and 34% an IQ of <20. Sixteen percent of the patients were non-ambulant. Regular laxative use was found in 26.4% (111/420) of the residents. In addition, occasional laxative use was found in 2% (10/420) of the residents. Oral laxatives were used daily by 13% (56/420) and oral laxatives daily in combination with enemas were used by 9% (39/420). Enemas but no oral laxatives were used by 3% (11/420); manual evacuation in combination with oral laxatives and enemas was used by 1% (5/420). Seventy-eight percent (78/100) of the oral laxative users used them for more than 1 year. Seventy-one percent (71/100) used one laxative, 23% two and 6% three. Thirty different brands of oral laxatives were used. Sixty-seven percent (67/100) used osmotic laxatives alone or in combination, 30% used stimulant laxatives, 19% used bulk forming laxatives and 19% mineral oil. Oral laxatives were always prescribed by attending physicians, while enemas were also initiated by nurses in 35% (18/52). Laxative use was positively and independently correlated with female gender, with being non-ambulant, with oral motor dysfunction and with the use of medication other than laxatives. It did not correlate with age. Within the institutions, laxative use varied from one to 15 users out of the 20 randomly selected patients (median 4/20). Laxative use is frequent in institutions for the mentally retarded, with a large inter-institution variation, indicating that constipation is an important problem and underlining the need for research into cost-effective treatment.
    European Journal of Clinical Pharmacology 02/1999; 54(12):965-9. DOI:10.1007/s002280050583 · 2.97 Impact Factor
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    R.H. Vander Stichele · B De Potter · P Vyncke · M.G. Bogaert ·
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    ABSTRACT: In Belgium, the distribution of medications to outpatients in community pharmacies is almost exclusively by branded unit-of-use packages, with a package insert inside every package. At the time of the study (spring 1990), the implementation of legislation that mandated a shift from highly technical documents to patient package inserts (PPIs), understandable by the lay person, had begun. This study explores the attitude of practising physicians toward written medication information for patients. A mail questionnaire was sent to 1500 (8% random sample) Belgian general practitioners and to 500 (22% random sample) internal medicine specialists. A total of 543 usable questionnaires were returned (27.5% return rate). Ninety-two percent of the physicians stated that their patients seldom or never requested additional information on drug efficacy or side effects, during routine consultation; 30% estimated that more than half of their patients read the PPI; 75% expect that a patient would experience side effects after reading about them in the PPI; 59% agreed that the PPI could help the patient react more adequately in unforeseen situations. It was possible to cluster the respondents in a stable segmentation of three clusters: moderately positive physicians (20%), ambiguous to neutral physicians (44%), physicians overtly negative to written drug information (36%). The low response rate to this extensive postal questionnaire limits the conclusions to a qualitative description of relevant clusters of respondents. In contrast with the opinion of physicians about patient readership, results from other studies indicate that the vast majority of patients read the package inserts.
    Patient Education and Counseling 07/1996; 28(1):5-13. DOI:10.1016/0738-3991(96)00866-X · 2.20 Impact Factor
  • Martine E. Laethem · Frans M. Belpaire · Marc G. Bogaert ·
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    ABSTRACT: The beta-blocking agent oxprenolol is used therapeutically as the racemate. In humans and animals it is metabolized i.a. to ether glucuronide diastereomers. A stereoselective HPLC assay was developed to determine directly, without hydrolysis to their parent enantiomers, the oxprenolol glucuronides in biological samples. The glucuronide standards for this direct assay are prepared by incubation of rabbit liver microsomes with RS-oxprenolol. The glucuronides obtained are purified and concentrated with solid-phase extraction, and their concentration is measured by an indirect method, i.e. HPLC assay of the oxprenolol enantiomers after enzymatic hydrolysis with beta-glucuronidase. The direct assay involves separation by HPLC using a C18-reversed-phase column, with UV detection at 274 nm; nalorphine is used as internal standard. On injection onto the column, without previous hydrolysis, the limit of detection is 20 ng for both glucuronides. The assay is sensitive, accurate and reproducible. The method is suitable for the assay of glucuronides in liver microsomal incubates and plasma.
    Journal of chromatography. B, Biomedical applications 02/1996; 675(2):251-5. DOI:10.1016/0378-4347(95)00358-4
  • F M Belpaire · M G Bogaert ·
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    ABSTRACT: In this review, after a short discussion of our knowledge about cytochrome P450 isoenzymes, two important sources of variability in the metabolism of drugs by cytochrome P450 are described, i.e. genetic factors and drug-drug interactions. Many hepatic cytochrome P450 enzymes play an important role in the oxidative biotransformation of numerous drugs and other foreign compounds, and of many endogenous substrates. In humans more than 20 different isoenzymes of cytochrome P450 responsible for the hepatic metabolism of drugs, have been identified. They are classified into families and subfamilies on the basis of the degree of amino acid similarity. Cytochrome P450 isoenzymes are regulated by both genetic and environmental factors. Of particular interest is genetic polymorphism in drug oxidation. Two genetic polymorphisms in drug oxidation are well known, the sparteine/debrisoquine (CYP2D6) polymorphism and the mephenytoin oxidation (CYP2C19) polymorphism. As a result of these polymorphisms, two phenotypes exist in the population, poor and extensive metabolizers. Poor metabolizers may be prone to adverse reactions towards drugs with a narrow therapeutic range. In extensive metabolizers clinically significant drug interactions between drugs metabolized by the same isoenzyme can occur.
    Acta clinica Belgica 02/1996; 51(4):254-60. · 0.59 Impact Factor
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    R H Vander Stichele · M G Bogaert · E Dezeure ·

  • M E Laethem · F M Belpaire · P Wijnant · M G Bogaert ·
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    ABSTRACT: To study the effect of probenecid on the stereoselective pharmacokinetics of oxprenolol and its glucuronides in the rabbit. An oral dose of 50 mg/kg racemic oxprenolol was given to nine rabbits twice, in random sequence with and without the concurrent administration of probenecid. Oxprenolol enantiomers were determined in plasma and urine by an enantioselective HPLC method. Oxprenolol glucuronides were measured in plasma and urine after enzymatic hydrolysis. The disposition of the oxprenolol enantiomers in rabbits is stereoselective, mainly due to a difference in metabolism. Renal excretion is only a minor elimination route for unchanged oxprenolol, and the renal clearances of the enantiomers are similar. Pretreatment with probenecid did not affect the plasma concentrations of the oxprenolol enantiomers, but there was a slight decrease in their urinary excretion. The plasma concentrations of the oxprenolol glucuronides are much higher than those of the parent enantiomers, and those of (S)-glucuronide are about twice those of its antipode. About 10% of the oxprenolol dose is excreted in the urine as glucuronides. The renal clearances of both glucuronides are similar, and markedly higher than the creatinine clearance. After probenecid, the mean glucuronide plasma levels were markedly higher, with for both glucuronides a more than twofold increase in mean AUC. Probenecid decreased the renal clearance of both glucuronides to about 30%. Moreover, it decreased slightly the formation clearance of (S)-glucuronide, while the formation clearance of (R)-glucuronide was not significantly influenced. Our results show that in the rabbit, both oxprenolol glucuronide diastereomers are actively secreted by the kidney, and that this process is inhibited by probenecid.
    Pharmaceutical Research 01/1996; 12(12):1964-7. DOI:10.1023/A:1016204309083 · 3.42 Impact Factor
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    Robert H Vander Stichele · Els M Dezeure · Marc G Bogaert ·
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    ABSTRACT: To collect and evaluate all trials on clinical efficacy of topical treatments for head lice. 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. Trials in schools or communities. Patients infested with lice. Cure rate (absence of live lice and viable nits) on day 14 after treatment. 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%. 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.
    BMJ Clinical Research 10/1995; 311(7005):604-8. DOI:10.1136/bmj.311.7005.604 · 14.09 Impact Factor
  • R H Vander Stichele · M G Bogaert ·

    The Lancet 04/1995; 345(8951):731; author reply 731-2. · 45.22 Impact Factor
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    ABSTRACT: Objective To study the pharmacokinetics of R(+)- and S(−)-oxprenolol and their corresponding glucuronide conjugates in healthy subjects.Methods An oral dose of 80 mg racemic oxprenolol was given to eight male volunteers. Venous blood samples and urine were collected as a function of time. Oxprenolol enantiomers in plasma and urine were determined by an enantiospecific HPLC method. Oxprenolol glucuronides in plasma and urine were measured as oxprenolol equivalents after enzymatic hydrolysis.ResultsFor R-oxprenolol the area under the plasma concentration—time curve was slightly higher (RS ratio, 1.19) and the oral clearance slightly lower (RS ratio, 0.84) than those parameters for S-oxprenolol. The free fraction of R-oxprenolol in plasma was 4% higher than that of S-oxprenolol. The intrinsic clearance of S-oxprenolol was 1.5 times larger than that of R-oxprenolol, and a maximum of 3% of the dose was excreted as unchanged enantiomers in the urine. The plasma concentrations of S-oxprenolol glucuronide were more than three times higher than those of R-oxprenolol glucuronide. Twenty-five percent of the dose of the R-enantiomer was excreted in the urine as R-oxprenolol glucuronide; 29% of the S-enantiomer dose was excreted as S-oxprenolol glucuronide. The renal clearance of R-oxprenolol glucuronide was, on average, 172 ml/min, suggesting active tubular secretion. In contrast, the renal clearance of S-oxprenolol glucuronide was only 49 ml/min, which can be explained by the plasma binding of the compound.Conclusions Our results show small differences in disposition between R- and S-oxprenolol but a marked difference in disposition between the glucuronides. The difference in plasma concentrations between the oxprenolol glucuronides is mainly attributable to the stereoselectivity of the renal excretion.Clinical Pharmacology & Therapeutics (1995) 57, 419-424; doi:
    Clinical Pharmacology &#38 Therapeutics 03/1995; 57(4):419-424. DOI:10.1016/0009-9236(95)90211-2 · 7.90 Impact Factor
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    F M Belpaire · P Wynant · P Van Trappen · M Dhont · A Verstraete · M G Bogaert ·
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    ABSTRACT: The protein binding of the enantiomers of propranolol and verapamil was measured in 19 pairs of maternal and foetal serum obtained at delivery. The binding of the enantiomers of both drugs was lower in foetal than in maternal serum. In maternal serum the mean (+/- s.d.) unbound percentages were 22.4 +/- 6.2 and 20.7 +/- 6.6 for R- and S-propranolol, and 16.8 +/- 5.5 and 22.5 +/- 6.2 for R- and S-verapamil; in foetal serum the values were 38.8 +/- 8.6 and 40.4 +/- 10.6 for R- and S-propranolol, and 34.7 +/- 10.5 and 44.8 +/- 10.7 for R- and S-verapamil. For propranolol, in maternal, but not in foetal serum, the difference between the binding of the R- and S-enantiomers was significant; the R/S ratio was significantly (P < 0.01) larger in the mother (1.099 +/- 0.072) than in the foetus (0.973 +/- 0.068). For verapamil, the difference in binding between the R- and S-enantiomers was significant in both maternal and foetal serum, but the R/S ratio was similar in mother (0.735 +/- 0.098) and foetus (0.763 +/- 0.070). Serum alpha 1-acid glycoprotein (AAG) concentrations were markedly higher and albumin concentrations slightly lower in maternal than in foetal samples. The binding of the four enantiomers in maternal and foetal serum was correlated (P < 0.001) with the AAG concentration (r propranolol: R 0.749, S 0.746; r verapamil: R 0.753, S 0.782). Our findings show that measurement of concentrations of total, unresolved drug allow a reasonably accurate assessment of transplacental gradients of individual isomers.
    British Journal of Clinical Pharmacology 02/1995; 39(2):190-3. DOI:10.1111/j.1365-2125.1995.tb04430.x · 3.88 Impact Factor
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    ABSTRACT: The influence of endotoxin-induced inflammation was studied on the pharmacokinetics of the enantiomers of the racemic drugs oxprenolol, propranolol, and verapamil in rabbits and dogs. Enantioselective pharmacokinetics were seen for oxprenolol and propranolol in the rabbit and for propranolol and verapamil in the dog. In the dog, the enantioselective differences in plasma concentrations are due to differences in both protein binding and metabolism, whereas in the rabbit the differences are due solely to differences in metabolism. In both species endotoxin treatment increases the plasma concentrations of the enantiomers of the three drugs; both protein binding and metabolism are influenced. In rabbits and in dogs, the influence of endotoxin on the disposition of the three drugs is less enantioselective than was previously observed in the rat.
    Chirality 01/1995; 7(8):616-22. DOI:10.1002/chir.530070811 · 1.89 Impact Factor
  • Robert H. Vander Stichele · Marc G. Vander Bogaert ·
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    ABSTRACT: In 1992 the European Community adopted Directive 92/27/EEC “On the labeling of medicinal products for human use and on package leaflets,” implementing the mandatory inclusion of full information leaflets written in understandable language in every medication package between January 1, 1994 and December 31, 1998. This article describes the features and historical motives of this new legislation. In addition, it reviews European research projects on the impact of written medication information.
    Therapeutic Innovation and Regulatory Science 01/1995; 29(1):285-290. DOI:10.1177/009286159502900130 · 0.46 Impact Factor
  • Marc G. Bogaert ·
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    ABSTRACT: The 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.(ABSTRACT TRUNCATED AT 250 WORDS)
    Cardiovascular Drugs and Therapy 11/1994; 8(5):693-9. DOI:10.1007/BF00877116 · 3.19 Impact Factor
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    ABSTRACT: The influence of endotoxin-induced inflammation on the enantioselective pharmacokinetics of propranolol, oxprenolol, and verapamil, which bind to alpha 1-acid glycoprotein, was studied in the rat. The racemic mixtures were given orally. In the control animals, for propranolol and oxprenolol, the plasma concentrations of the (R)-enantiomer were higher than those of the (S)-enantiomer, while for verapamil the reverse was true. Protein binding and intrinsic clearance are the main factors responsible for this enantioselectivity. After endotoxin treatment, for the three drugs tested the plasma concentrations and the plasma binding of both enantiomers were significantly increased. This effect was more pronounced for (R)-propranolol, (R)-oxprenolol, and (S)-verapamil than for their respective antipodes. The enantioselective effect of endotoxin on the plasma concentrations of the drugs studied seems mainly due to the enantioselective increase in binding to alpha 1-acid glycoprotein.
    Chirality 02/1994; 6(5):405-10. DOI:10.1002/chir.530060508 · 1.89 Impact Factor
  • A M Vermeulen · F M Belpaire · F De Smet · I Vercruysse · M G Bogaert ·
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    ABSTRACT: After i.v. administration of racemic metoprolol in the rat, the plasma concentrations of(R)- and (S)-metoprolol were comparable, and no differences in pharmacokinetic parameters between the two enantiomers were found. From the 3rd to the 12th month, comparable changes were seen for both enantiomers: there was an increase in the area under the plasma concentration-time curve (AUC) and a decrease in blood and plasma clearance. Half-life showed a significant prolongation, volume of distribution decreased between 3 and 12 months and increased between 12 and 24 months. After oral administration of the racemate, AUC and Cmax (maximum plasma concentration) were slightly higher, while oral clearance was slightly lower for (R)-metoprolol than for (S)-metoprolol. With aging, Cmax and AUC increased for both enantiomers, while oral clearance decreased. The change in oral clearance as a function of age is different between (S)- and (R)-metoprolol, and thus enantioselective. In vitro disappearance rate in 3-month-old rats was significantly higher for (S)-metoprolol than for (R)-metoprolol, although the difference was small. With aging, the disappearance rates of both enantiomers increased significantly, but not enantioselectively.
    Journal of Gerontology 06/1993; 48(3):B108-14. DOI:10.1093/geronj/48.3.B108

Publication Stats

3k Citations
553.28 Total Impact Points


  • 1971-2001
    • Ghent University
      • • Department of Pharmacology
      • • Department of Internal Medicine
      Gand, Flanders, Belgium
  • 1972-2000
    • Universitair Ziekenhuis Ghent
      • Department of Neurology
      Gand, Flanders, Belgium
  • 1992
    • Universitair Ziekenhuis Leuven
      • Department of Emergency medicine
      Louvain, Flanders, Belgium
  • 1978
    • Catholic University of Louvain
      • Laboratory of Hepatogastroenterology
      Walloon Region, Belgium
  • 1977
    • University of Leuven
      • Division of Hypertension and Cardiovascular
      Louvain, Flanders, Belgium