References of "Vrijens, Bernard"
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See detailProjected inhibition of platelet aggregation with ticagrelor twice daily vs. clopidogrel once daily based on patient adherence data (the TWICE project)
Vrijens, Bernard ULg; Claeys, M.J.; LEGRAND, Victor ULg et al

in British Journal of Clinical Pharmacology (2014), 77(5), 746-755

Abstract Aim Twice daily dosing is often perceived as inferior to once daily dosing due to a higher likelihood of missing a dose. However, more important is the extent to which drug action is maintained ... [more ▼]

Abstract Aim Twice daily dosing is often perceived as inferior to once daily dosing due to a higher likelihood of missing a dose. However, more important is the extent to which drug action is maintained when doses are delayed or missed. We compared the estimated inhibition of platelet aggregation (eIPA) for ticagrelor twice daily and clopidogrel once daily, based on their pharmacokinetic/ pharmacodynamic relationships and patient dosing history data. Methods Drug dosing histories of 5014 patients prescribed cardiovascular medications (primarily antihypertensive medicines) were extracted from an electronically compiled dosing history database. eIPA levels were simulated for 677 twice daily and 677 once daily dosing histories over a 30 day period, based on published onset/offset models for ticagrelor and clopidogrel IPA characteristics. Results While many patients treated twice daily missed at least one dose in 30 days, only 25.7% missed two consecutive doses. By comparison, 46.8% of patients treated once daily missed at least one dose. Simulations based on patient adherence over time showed that the average mean eIPA for ticagrelor twice daily remained significantly higher than for clopidogrel once daily (81.1% vs. 55.0%, P < 0.001). Ticagrelor twice daily patients had an eIPA below 10% for 0.20% of the 30 day period compared with 2.05% for clopidogrel once daily (P = 0.0001). Conclusions The projected level of platelet inhibition remained higher for ticagrelor twice daily than clopidogrel once daily, mainly due to the higher eIPA level achieved with ticagrelor and the relatively low likelihood of missing two consecutive twice daily doses. This modelling and simulation study suggests a therapeutic benefit of ticagrelor over clopidogrel when taking into account the most common dosing omissions. © 2013 The British Pharmacological Society. [less ▲]

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See detailEstimation of HIV treatment-efficacy by combining structural nested mean models with pharmacokinetic models of antiretroviral drug exposure
Comté, Laetitia ULg; Vansteelandt, Stijn; Rode, Richard et al

in Statistics and its interface (2011), 4(4), 511-520

The aim of treating HIV-1-infected patients is to achieve and maintain suppression of viral load (VL). Achievement of this aim is thwarted by variable adherence to prescribed anti-retroviral drugs ... [more ▼]

The aim of treating HIV-1-infected patients is to achieve and maintain suppression of viral load (VL). Achievement of this aim is thwarted by variable adherence to prescribed anti-retroviral drugs. Variable adherence to an antiretroviral regimen creates variability in the patient’s internal exposure to the drugs. Structural nested mean models (SNMMs) enabled us to estimate, during the initial phase of treatment, the relationship between variable internal exposure and VL, accounting for measured time-varying confounders and feedback relations using an antiretroviral regimen containing lopinavir/ritonavir (LPV/RTV, LPV/r). Our final SNMM predicts that the short term effect of treatment is modified by the most recent past VL, with higher initial VL’s being associated with larger treatment-induced reductions in VL for a given internal exposure to the drugs. Variation in internal exposure to LPV/r in the interquartile interval (P25%–P75%) only slightly affects the overall reduction in VL, supporting the conclusion that the relatively long duration of action of LPV/r lessens the impact on VL of the most frequently recurring intermittent lapses in dosing. [less ▲]

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See detailEstimation of the comparative therapeutic superiority of QD and BID dosing regimens, based on integrated analysis of dosing history data and pharmacokinetics
Comté, Laetitia ULg; Vrijens, Bernard ULg; Tousset, Eric et al

in Journal of Pharmacokinetics and Pharmacodynamics (2007), 34(4), 549-558

Once-daily dosing almost invariably shows a slightly higher percentage of prescribed doses taken than does twice-daily dosing. Many pharmaceutical scientists, regulators, and prescribers have considered ... [more ▼]

Once-daily dosing almost invariably shows a slightly higher percentage of prescribed doses taken than does twice-daily dosing. Many pharmaceutical scientists, regulators, and prescribers have considered this finding to signify the therapeutic superiority of once-daily dosing. The therapeutically more relevant question, however, is not the percentage of prescribed doses taken but the comparative impact of missed doses on the pharmacologic effects of a drug under the two dosing regimens. A key point in this regard is that the pharmacokinetic equivalent of a single missed once-daily dose is 2-3 sequentially omitted twice-daily doses. Thus, an important parameter in comparing the two regimens is the probability of two or three twice-daily doses being sequentially omitted, versus the probability of missing a single once-daily dose. Our data indicate that the probability of sequential omission of 2-3 twice daily doses is half the probability of omission of a single once-daily dose. For that reason, a twice-daily regimen could prove to be superior to a once-daily regimen in maintaining drug concentrations within a therapeutically desirable range. A more important consideration, however, is to maintain not just the concentration of drug in plasma, but the drug's therapeutic action. The duration of therapeutic drug action following a last-taken dose is not only drug-specific, but also, for some drug, dependent on the pharmacodynamic properties. Judging the comparative superiority of one dosing regimen over another requires knowledge of the drug's duration action after a last-taken dose, plus knowledge of the comparative probabilities of the various patterns of dose omission. When applied to HIV protease inhibitors, a twice-daily regimen appears to be better than an once-daily regimen in maintaining therapeutically effective drug actions. [less ▲]

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See detailPsychological Approaches During Conscious Sedation. Hypnosis Versus Stress Reducing Strategies: A Prospective Randomized Study
Faymonville, Marie-Elisabeth ULg; Mambourg, P. H.; Joris, Jean ULg et al

in Pain (1997), 73(3), 361-7

Stress reducing strategies are useful in patients undergoing surgery. Hypnosis is also known to alleviate acute and chronic pain. We therefore compared the effectiveness of these two psychological ... [more ▼]

Stress reducing strategies are useful in patients undergoing surgery. Hypnosis is also known to alleviate acute and chronic pain. We therefore compared the effectiveness of these two psychological approaches for reducing perioperative discomfort during conscious sedation for plastic surgery. Sixty patients scheduled for elective plastic surgery under local anesthesia and intravenous sedation (midazolam and alfentanil upon request) were included in the study after providing informed consent. They were randomly allocated to either stress reducing strategies (control: CONT) or hypnosis (HYP) during the entire surgical procedure. Both techniques were performed by the same anesthesiologist (MEF). Patient behavior was noted during surgery by a psychologist, the patient noted anxiety, pain, perceived control before, during and after surgery, and postoperative nausea and vomiting (PONV). Patient satisfaction and surgical conditions were also recorded. Peri- and postoperative anxiety and pain were significantly lower in the HYP group. This reduction in anxiety and pain were achieved despite a significant reduction in intraoperative requirements for midazolam and alfentanil in the HYP group (alfentanil: 8.7 +/- 0.9 microg kg(-1)/h(-1) vs. 19.4 +/- 2 microg kg(-1)/h(-1), P < 0.001; midazolam: 0.04 +/- 0.003 mg kg(-1)/h(-1) vs. 0.09 +/- 0.01 mg kg(-1)/h(-1), P < 0.001). Patients in the HYP group reported an impression of more intraoperative control than those in the CONT group (P < 0.01). PONV were significantly reduced in the HYP group (6.5% vs. 30.8%, P < 0.001). Surgical conditions were better in the HYP group. Less signs of patient discomfort and pain were observed by the psychologist in the HYP group (P < 0.001). Vital signs were significantly more stable in the HYP group. Patient satisfaction score was significantly higher in the HYP group (P < 0.004). This study suggests that hypnosis provides better perioperative pain and anxiety relief, allows for significant reductions in alfentanil and midazolam requirements, and improves patient satisfaction and surgical conditions as compared with conventional stress reducing strategies support in patients receiving conscious sedation for plastic surgery. [less ▲]

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See detailPlasma Estradiol Concentrations and Pharmacokinetics Following Transdermal Application of Menorest 50 or Systen (Evorel) 50
Reginster, Jean-Yves ULg; Albert, Adelin ULg; Deroisy, Rita ULg et al

in Maturitas (1997), 27(2), 179-86

OBJECTIVES: In order to compare the pharmacokinetics of two transdermal estrogen replacement therapy (ERT) systems designed to release 50 micrograms 17 beta-estradiol/day, two studies were performed in ... [more ▼]

OBJECTIVES: In order to compare the pharmacokinetics of two transdermal estrogen replacement therapy (ERT) systems designed to release 50 micrograms 17 beta-estradiol/day, two studies were performed in healthy postmenopausal volunteers. METHODS: Both studies had a cross-over design and incorporated a 1-week wash-out period between treatments. In the first study, Menorest 50 and Systen 50 (Evorel 50) were compared over four days of application in 30 women. In the second, 13 women wore each of the two systems for a total of 12 days each (three patches each for 4 days), and comparison was made during the third patch period (steady state, between days 8 and 12). Plasma 17 beta-estradiol levels were assayed using specific direct radioimmunoassays, and pharmacokinetic parameters were calculated by standard methods. All the samples of the first study were re-analysed using a different radioimmunoassay and the results of both assays were compared. RESULTS: In both studies, plasma 17 beta-estradiol levels rose at a comparable rate and reached similar peak levels with each of the two formulations. Levels then remained relatively constant throughout both evaluation periods with Menorest 50, but began to decline after 12 hours in the first study and after 30 h under steady state conditions in the second study with Systen 50. The difference between the two products was statistically significant in both studies. Analysis of pharmacokinetic parameters confirmed the greater bioavailability of Menorest 50. In addition, 17 beta-estradiol levels remained within the suggested therapeutic ranges for relief of acute symptoms and protection against osteoporosis for longer periods of time with Menorest 50 than with Systen 50. CONCLUSION: Since the acute efficacy, long-term protective effects, side effects and risks associated with ERT may depend on critical threshold plasma levels, much attention should be paid to the pharmacokinetic profiles of different formulations. The comparison of these two different radioimmunoassays demonstrates the comparability of their results. [less ▲]

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See detailEffect of potassium channel openers on the firing rate of hippocampal pyramidal cells and A10 dopaminergic neurons in vitro.
Scuvée-Moreau, Jacqueline ULg; Seutin, Vincent ULg; Vrijens, Bernard ULg et al

in Archives of Physiology & Biochemistry (1997), 105(5), 421-8

The effect of four KATP channel openers (KCOs) on the firing rate of CA1 pyramidal cells and A10 dopaminergic neurons was investigated using extracellular recording techniques in rat brain slices ... [more ▼]

The effect of four KATP channel openers (KCOs) on the firing rate of CA1 pyramidal cells and A10 dopaminergic neurons was investigated using extracellular recording techniques in rat brain slices. Pinacidil, lemakalim, diazoxide and a new compound, BPDZ44, had an inhibitory effect on the electrical activity of CA1 pyramidal cells. They all had a similar potency. Only BPDZ44 and diazoxide inhibited the firing rate of A10 dopamine neurons. The sulfonylurea glipizide (1 microM) antagonized the effect of BPDZ44 and diazoxide on A10 neurons but failed to antagonize the effect of KCOs on CA1 pyramidal cells. These results show that differences exist among KCOs in their ability to decrease the electrical activity of various populations of central neurons. [less ▲]

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See detailEffect of Propofol on in Vitro Lipid Peroxidation Induced by Different Free Radical Generating Systems: A Comparison with Vitamin E
Hans, Pol ULg; Deby, Christiane ULg; Deby-Dupont, G. et al

in Journal of Neurosurgical Anesthesiology (1996), 8(2), 154-8

Propofol has been reported to have antioxidant properties and to inhibit lipid peroxidation. In this study, we examined the ability of propofol to inhibit lipid peroxidation induced by three free radical ... [more ▼]

Propofol has been reported to have antioxidant properties and to inhibit lipid peroxidation. In this study, we examined the ability of propofol to inhibit lipid peroxidation induced by three free radical systems (hydroxyl, ferryl, and oxo-ferryl radicals), and we compared the effect of propofol with that of vitamin E, an endogenous antioxidant. Lipid peroxidation was induced by exposing a linoleic acid emulsion to either water gamma radiation, a ferrous iron-ascorbate solution, or human hemoglobin, generating the hydroxyl, ferryl, and oxo-ferryl radicals, respectively. Each experiment was performed in triplicate with and without propofol or vitamin E at concentrations between 10(-5) and 10(-4) M. Lipid peroxidation was quantified by gas chromatography measurement of the pentane released (nmoles) from lipid decomposition. In each condition, a significant dose-response relationship was found between the release of pentane and the concentration of either propofol or vitamin E. The antioxidant activities of both agents were similar but significantly higher against the hydroxyl than the ferryl and oxo-ferryl radicals. The study suggests that propofol could be beneficial as an anesthetic or sedative drug in patients presenting pathologies associated with free radical reactions. [less ▲]

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See detailPlasma Concentration of Estradiol Following Transdermal Administration of Systen 50 or Menorest 50
Reginster, Jean-Yves ULg; Albert, Adelin ULg; Deroisy, Rita ULg et al

in Scandinavian Journal of Rheumatology. Supplement (1996), 103

Circulating levels of 17 beta estradiol (E2) following the administration of fixed doses of E2, show a great variability in kinetics depending upon the product administrated, the routes of administration ... [more ▼]

Circulating levels of 17 beta estradiol (E2) following the administration of fixed doses of E2, show a great variability in kinetics depending upon the product administrated, the routes of administration, and the interindividual variations in absorption and metabolism. This might have important implications both in terms of tolerance and effectiveness. Two new forms of transdermal E2 (SYSTEN Cilag and MENOREST Rhone-Poulenc Rorer) have been recently accepted in Europe for the treatment of climacteric symptoms. The present study was undertaken to compare the pharmacokinetic characteristics of plasma E2 profile under these two drugs. It was carried out in 30 healthy postmenopausal volunteers according to good clinical practice after informed consent, as a single blind, randomised, cross-over study during the classical wearing period of 4 days. Plasma E2 concentration was determined 24 hours before, 1/2 hour before and then 2, 4, 8, 12, 24, 48, 72, 84, 96 hours after the first patch administration. E2 measurement was performed using a specific direct radioimmunoassay developed in the FRH laboratories. The main criteria for this method were an intraassay coefficient of variation (CV) less than 6%, an interassay CV less than 8% in a concentration range of 15-140 pg/ml and a quantitative detection limit (LOQ) of 2.7 pg/ml with a 20% CV. The following kinetic parameters were analysed: C(max), C(mean), C96 and MRT. The bioequivalence was assessed by analysis of variance of C(max), C(mean), C96 and AuC after logarithmic transformation, complemented by Westlake test (95%). Data show that these two products are identical in terms of C(max) but C(mean), C96 and AuC are statistically greater when MENOREST 50(R) is administered; furthermore, E2 levels decrease more rapidly and more deeply with SYSTEN 50 than MENOREST 50. The differences of pharmacokinetic profiles after administration of two different forms of the same dose of 50 micrograms transdermal 17 beta estradiol might have important medical consequences. [less ▲]

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