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See detailPharmacokinetics and pharmacological properties of two galenical preparations of glibenclamide, HB419 and HB420, in non insulin-dependent (type 2) diabetes.
Scheen, André ULg; Jaminet, C.; Luyckx, A. S. et al

in International Journal of Clinical Pharmacology, Therapy, and Toxicology (1987), 25(2), 70-6

The pharmacokinetics and pharmacological properties of a new micronized preparation of glibenclamide (HB420, 3.5 mg/tablet) were compared to those of the classical formulation (HB419, 5 mg/tablet) in non ... [more ▼]

The pharmacokinetics and pharmacological properties of a new micronized preparation of glibenclamide (HB420, 3.5 mg/tablet) were compared to those of the classical formulation (HB419, 5 mg/tablet) in non insulin-dependent diabetics. In a double-blind cross-over randomized acute study, blood glucose, plasma insulin, C-peptide and glibenclamide levels were determined in 10 patients after a standardized breakfast taken 15 min following the ingestion of 1.1 +/- 0.2 tablets of HB419 or HB420. Plasma glibenclamide levels rose faster, the peak value was higher (637 +/- 154 versus 411 +/- 76 nmol/l, p less than 0.05) and the area under the curve from 0 to 240 min was 35% greater (p less than 0.05) on HB420 than on HB419. Nevertheless, the post-breakfast hormonal and metabolic changes were similar with both preparations. In a single-blind cross-over chronic study, 12 patients were treated during 3 successive 6 to 8-week periods--HB419, HB420, HB419--with glibenclamide at a dose of 1.8 +/- 0.3 tablets/day. While fasting blood glucose concentrations remained unchanged throughout the study, postprandial levels decreased from 10.9 +/- 0.8 mmol/l during the HB419 pre-period to 9.2 +/- 0.6 mmol/l during HB420 (p less than 0.02) and rose again up to 10.4 +/- 0.8 mmol/l during the last HB419 period (p less than 0.05). Similarly HbA1c decreased slightly from 7.4 +/- 0.3 to 7.2 +/- 0.4% (NS) and increased again up to 7.8 +/- 0.4% (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

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See detailPharmacokinetics for once- versus twice-daily tacrolimus formulations in de novo kidney transplantation: a randomized, open-label trial.
Wlodarczyk, Z.; Squifflet, Jean-Paul ULg; Ostrowski, M. et al

in American Journal of Transplantation (2009), 9(11), 2505-13

Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may ... [more ▼]

Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC(0-24) of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC(0-24) and C(min) for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID. [less ▲]

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See detailPharmacokinetics in patients with chronic liver disease and hepatic safety of incretin-based therapies for the management of type 2 diabetes mellitus.
Scheen, André ULg

in Clinical pharmacokinetics (2014), 53(9), 773-85

Patients with type 2 diabetes mellitus have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis, and about one-third of cirrhotic patients have ... [more ▼]

Patients with type 2 diabetes mellitus have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis, and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents, such as metformin and sulphonylureas, may be a concern in case of hepatic impairment (HI). New glucose-lowering agents targeting the incretin system are increasingly used for the management of type 2 diabetes. Incretin-based therapies comprise oral inhibitors of dipeptidyl peptidase-4 (DPP-4) (gliptins) or injectable glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review summarises the available data regarding the use of both incretin-based therapies in patients with HI. In contrast to old glucose-lowering agents, they were evaluated in specifically designed acute pharmacokinetic studies in patients with various degrees of HI and their hepatic safety was carefully analysed in large clinical trials. Only mild changes in pharmacokinetic characteristics of DPP-4 inhibitors were observed in patients with different degrees of HI, presumably without major clinical relevance. GLP-1 receptor agonists have a renal excretion rather than liver metabolism. Specific pharmacokinetic data in patients with HI are only available for liraglutide. No significant changes in liver enzymes were reported with DPP-4 inhibitors or GLP-1 receptor agonists, alone or in combination with various other glucose-lowering agents, in clinical trials up to 2 years in length. On the contrary, preliminary data suggested that incretin-based therapies may be beneficial in patients with CLD, more particularly in the presence of non-alcoholic fatty liver disease. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, because of a lack of clinical experience with incretin-based therapies in these vulnerable patients. [less ▲]

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See detailPharmacokinetics of dipeptidylpeptidase-4 inhibitors.
Scheen, André ULg

in Diabetes, Obesity & Metabolism (2010), 12(8), 648-58

Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control ... [more ▼]

Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control, without inducing hypoglycaemia or weight gain. Dipeptidylpeptidase-4 (DPP-4) inhibitors are new oral glucose-lowering agents, so-called incretin enhancers, which may be used as monotherapy or in combination with other antidiabetic compounds. Sitagliptin, vildaglipin and saxagliptin are already on the market in many countries, either as single agents or in fixed-dose combined formulations with metformin. Other DPP-4 inhibitors, such as alogliptin and linagliptin, are currently in late phase of development. The present paper summarizes and compares the main pharmacokinetics (PK) properties, that is, absorption, distribution, metabolism and elimination, of these five DPP-4 inhibitors. Available data were obtained in clinical trials performed in healthy young male subjects, patients with T2DM, and patients with either renal insufficiency or hepatic impairment. PK characteristics were generally similar in young healthy subjects and in middle-aged overweight patients with diabetes. All together gliptins have a good oral bioavailability which is not significantly influenced by food intake. PK/pharmacodynamics characteristics, that is, sufficiently prolonged half-life and sustained DPP-4 enzyme inactivation, generally allow one single oral administration per day for the management of T2DM; the only exception is vildagliptin for which a twice-daily administration is recommended because of a shorter half-life. DPP-4 inhibitors are in general not substrates for cytochrome P450 (except saxagliptin that is metabolized via CYP 3A4/A5) and do not act as inducers or inhibitors of this system. Several metabolites have been documented but most of them are inactive; however, the main metabolite of saxagliptin also exerts a significant DPP-4 inhibition and is half as potent as the parent compound. Renal excretion is the most important elimination pathway, except for linagliptin whose metabolism in the liver appears to be predominant. PK properties of gliptins, combined with their good safety profile, explain why no dose adjustment is necessary in elderly patients or in patients with mild to moderate hepatic impairment. As far as patients with renal impairment are concerned, significant increases in drug exposure for sitagliptin and saxagliptin have been reported so that appropriate reductions in daily dosages are recommended according to estimated glomerular filtration rate. The PK characteristics of DPP-4 inhibitors suggest that these compounds are not exposed to a high risk of drug-drug interactions. However, the daily dose of saxagliptin should be reduced when coadministered with potent CYP 3A4 inhibitors. In conclusion, besides their pharmacodynamic properties leading to effective glucose-lowering effect without inducing hypoglycaemia or weight gain, DPP-4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice. [less ▲]

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See detailPharmacokinetics of imipramine in narcoleptic horses
Delguste, Catherine ULg

Conference given outside the academic context (2007)

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See detailPharmacokinetics, pharmacodynamics, and safety of pasireotide LAR in patients with acromegaly: A randomized, multicenter, open-label, phase I study.
Petersenn, Stephan; Bollerslev, Jens; Arafat, Ayman M. et al

in Journal of Clinical Pharmacology (2014), 54(11), 1308-1317

Pasireotide (SOM230), a multireceptor-targeted somatostatin analogue, has exhibited favorable safety/tolerability in several clinical studies. A long-acting-release (LAR) formulation of pasireotide may ... [more ▼]

Pasireotide (SOM230), a multireceptor-targeted somatostatin analogue, has exhibited favorable safety/tolerability in several clinical studies. A long-acting-release (LAR) formulation of pasireotide may offer advantages over the subcutaneous formulation. This randomized, open-label, Phase I study evaluated the safety, PK, and PD of pasireotide LAR 20, 40, or 60 mg/month in patients with acromegaly. Safety assessments and blood samples for PK and PD were taken at designated time points. Thirty-five patients were randomized and completed the study. Steady-state pasireotide concentrations were achieved following three monthly injections. Trough pasireotide concentrations (ng/mL) 28 days after each injection were: 2.48, 4.16, and 3.10 (20 mg group); 6.42, 6.62, and 7.12 (40 mg group); and 9.51, 11.7, and 13.0 (60 mg group). At study end, 51% and 57% of patients achieved GH levels </=2.5 mug/L and IGF-1 levels below ULN, respectively. Compared with baseline, fasting blood glucose and HbA1c levels increased, whereas fasting blood insulin levels decreased. Acromegaly symptoms were generally improved. Adverse events were mostly gastrointestinal and mild/moderate. Pasireotide LAR was generally well tolerated. Steady-state PK was achieved after three monthly doses; exposures were approximately dose proportional. Control of GH, IGF-1, and symptoms improved, suggesting that pasireotide LAR may be an effective treatment for acromegaly. [less ▲]

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Peer Reviewed
See detailPharmacologic treatment of inner ear: from basic science to the patient.
Lefèbvre, Philippe ULg; Staecker, H.; Van de Water, T. et al

in Acta Oto-Rhino-Laryngologica Belgica (2002), 56(1), 45-9

Most of the deafness are of sensorineural origin and are characterized by a loss of hair cells and of spiral ganglion neurons. At the present time, hearing aids are the only treatment. However, in some ... [more ▼]

Most of the deafness are of sensorineural origin and are characterized by a loss of hair cells and of spiral ganglion neurons. At the present time, hearing aids are the only treatment. However, in some diseases of the inner ear, pharmacological treatment have been proposed and used successfully. In this paper, we will review some basic science aspects of the biology of the neurosensory structures of the inner ear, in particular of the auditory neurons, that lead to the rationale of some treatments for the inner ear diseases. Developmental studies, neuronal cell culture experiments, and analyses of gene knockout animals reveal a number of growth factors which are important for the rescue and repair of injured auditory neurons in the inner ear. These factors rescue the injured auditory neurons in vivo. Furthermore, perfusion of antioxydant to the cochlea prevented the hearing loss induced by cisplatin. These in vitro and in vivo experiments demonstrate that it is possible to manipulate the neurosensory structures of the inner ear and provide an effective treatment to prevent the degeneration of the neurons. The molecules or drugs can be administered locally to the inner ear through a direct perilymphatic perfusion or through the round window membrane. As an example, we will discuss the treatment of patients suffering from idiopathic sensorineural hearing loss which can be treated successfully by a perfusion through the round window membrane, improving their hearing threshold and their speech discrimination. [less ▲]

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See detailPharmacologic treatment of obesity, food intake, and reversal of metabolic disorders.
SCHEEN, André ULg; PAQUOT, Nicolas ULg

in Current Research in Nutrition & Food intake (2007), 3

The present paper is reviewing the current place of weight-reducing drugs in the overall management of overweight/obese subjects, especially those with metabolic disorders and type 2 diabetes. Anti ... [more ▼]

The present paper is reviewing the current place of weight-reducing drugs in the overall management of overweight/obese subjects, especially those with metabolic disorders and type 2 diabetes. Anti-obesity agents should be carefully evaluated in long-term (1-2 years) randomized controlled trials. Recent systematic reviews and meta-analysis assessed both the safety and efficacy of the two drugs currently used in the treatment of obesity, i.e. orlistat, a gastric and pancreatic lipase inhibitor that reduces fat absorption from the gut, and sibutramine, a combined norepinephrine and serotonin reuptake inhibitor that regulates food intake. Rimonabant, a new compound acting as selective blocker of CB1 receptors of the endocannabinoid system, raises much interest as it promotes weight reduction by a central effect and also exerts peripheral effects targeting cardiometabolic risk. Special attention will be paid to beneficial metabolic effects resulting from (even moderate) weight loss and to possible additional effects beyond weight reduction. [less ▲]

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See detailPharmacological analysis of ATP-dependent potassium channel openers on the vascular smooth muscle
Fontaine, J.; Pirotte, Bernard ULg; Lebrun, P.

Poster (1997, February 15)

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See detailPharmacological analysis of ATP-dependent potassium channels openers on vascular smooth muscle
Ouedraogo, R.; Somers, F.; De Tullio, Pascal ULg et al

Conference (1997, April)

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See detailPharmacological characterization of N-tert-butyl-N’-[2-(4’-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a novel thromboxane A2 receptor antagonist and thromboxane synthase inhibitor in a rat model of arterial thrombosis and its effects on bleeding time
Dogné, Jean-Michel ULg; Hanson, Julien ULg; De leval, X. et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2004), 309(2), 498-505

The present study was undertaken to characterize the antiplatelet and antithrombotic effects of BM-573 [N-tert-butyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl] urea], an original combined ... [more ▼]

The present study was undertaken to characterize the antiplatelet and antithrombotic effects of BM-573 [N-tert-butyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl] urea], an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor in rats, and to determine its effects on mice bleeding time. Intraperitoneal injection of a single dose of 5 mg/kg BM-573 to rats inhibited U-46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin F-2)-induced washed platelet aggregation 30 min and 1, 2, and 4 h after drug administration with a maximum antiplatelet effect observed after 1 and 2 h. In a rat model of thrombosis induced by ferric chloride application on the abdominal aorta, BM-573 significantly reduced the thrombus weight by 92.53, 80.20, 64.75, and 18.21% at doses of 5, 2, 0.5, and 0.2 mg/kg, respectively. Time to occlusion of abdominal aorta in the BM-573-treated group (41.50+/-5.21 min) was significantly prolonged compared with the vehicle-treated rats (16.16+/-0.79 min). Like furegrelate, seratrodast, and acetylsalicylic acid, BM-573 did not affect the tail bleeding time induced by tail transection in mice compared with vehicle-treated mice. Moreover, BM-573, a close derivative of the loop diuretic torasemide, failed to induce a significant increase in diuresis in rat and did not produce a decrease in blood glucose concentration as observed with the sulfonylurea glibenclamide. In conclusion, we have demonstrated that the nitrobenzenic sulfonylurea BM-573, an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor, is a potent antithrombotic agent that does not affect bleeding time. Moreover, BM-573 lost the diuretic property of torasemide and has no impact on glycemia. [less ▲]

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See detailPharmacological characterization of the enhancement of apomorphine-induced gnawing in mice by cocaine
Tirelli, Ezio ULg; Witkin, J. M.

in Pharmacology, Biochemistry & Behavior (1996), 55(1), 135-140

Characterized the behavioral and pharmacological mechanisms associated with cocaine potentiation of apomorphine (AP)-induced gnawing (AIG) in male C57BL/6J mice. Results showed that (-)-cocaine enhanced ... [more ▼]

Characterized the behavioral and pharmacological mechanisms associated with cocaine potentiation of apomorphine (AP)-induced gnawing (AIG) in male C57BL/6J mice. Results showed that (-)-cocaine enhanced AIG at doses devoid of effects on gnawing when given alone; (+)-cocaine or (-)-cocaine methiodide were also devoid of effects. Lidocaine, a local anesthetic without prominent dopaminergic actions, augmented the gnawing response to AP without increasing climbing or gnawing when given alone. (+)-Amphetamine enhanced AIG gnawing but only at a high dose that increased gnawing by itself. The selective dopamine (DA) uptake blocker, GBR 12909, augmented AIG by itself; however, it increased climbing at doses that augmented the gnawing response. These data indicate that the cocaine-augmented gnawing response to AP may be due to blockade of DA uptake and or the local anesthetic actions of cocaine. ((c) 1997 APA/PsycINFO, all rights reserved) [less ▲]

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See detailPharmacological effects of tiludronate in horses after immobilisation
Delguste, Catherine ULg; Lepage, Olivier M; Doucet, Michèle et al

Poster (2006)

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See detailPharmacological effects of tiludronate in horses after long-term immobilization
Delguste, Catherine ULg; Amory, Hélène ULg; Doucet, Michèle et al

in BONE (2007), 41(3), 414-421

Introduction: Tiludronate, a bisphosphonate, has recently been introduced in veterinary medicine to treat orthopedic conditions in the horse. This study was designed to evaluate its effects on biochemical ... [more ▼]

Introduction: Tiludronate, a bisphosphonate, has recently been introduced in veterinary medicine to treat orthopedic conditions in the horse. This study was designed to evaluate its effects on biochemical biomarkers of bone metabolism and on bone density and structure in an experimental model of disuse osteoporosis induced by cast application in horses. Methods: Two groups of eight horses were immobilized during 8 weeks. The first group (P-group) received a placebo, and the second group (T-group) received tiludronate 1 mg/kg by slow IV infusion. Both treatments were administered twice, 28 days apart. Immobilization consisted of stall rest with the left forelimb packed in a fiberglass cast. It was followed by a 4-week remobilization period and an 8-week standardized training protocol. One biomarker of bone resorption, the C-telopeptides of type 1 collagen cross-links (CTX-1) and one biomarker of bone formation, the bone isoenzyme of alkaline phosphatase (bone ALP), were assessed. Metacarpus III (MCIII) bone mineral density (BMD) and speed of sound (SOS) were evaluated respectively by dual energy X-ray absorptiometry (DEXA) and quantitative ultrasonography (QUS). Lameness was regularly assessed during the remobilization and training periods. Group- and time-related effects were tested by analysis of variance on repeated measurements. Results: A rapid, transient and significant decrease in CTX-1 concentration was seen after each treatment in the T-group only. No significant differences between groups were seen in the evolution of bone ALP activity. At the end of the experiment, the loss of MCIII BMD measured by DEXA in the immobilized limb was significantly less in the T-group than in the P-group. The MCIII SOS measured by QUS did not significantly vary within or between groups throughout the study. Discussion and conclusions: Tiludronate was found to significantly reduce bone resorption during immobilization, as well as to prevent long-term osteopenia in the immobilized limb. Disuse osteopenia did not affect the lateral superficial cortex of MCIII. (C) 2007 Elsevier Inc. All rights reserved. [less ▲]

Detailed reference viewed: 27 (1 ULg)
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See detailPharmacological evaluation of 3-alkylsulfanyl-4H-1,2,4-benzothiadiazine 1,1-dioxides structurally related to the KATP channel opener diazoxide
Boverie, S.; Nguyen, Q.-A.; De Tullio, Pascal ULg et al

in Fundamental & Clinical Pharmacology (1999), 13

Detailed reference viewed: 4 (0 ULg)
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See detailPharmacological evaluation of 4,6-disubstituted 2,2-dimethylchromans structurally related to the KATP channel opener cromakalim
Sebille, S.; Becker, B.; Antoine, M. H. et al

Poster (2000, November 18)

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See detailPharmacological evaluation of BM-573, a dual thromboxane A(2) receptor antagonist and thromboxane synthase inhibitor, as potential anti-metastatic agent
de Leval, X. J.; Dassesse, T.; Benoit, V. et al

in Blood (2003, November 16), 102(11, Part 2), 72

Detailed reference viewed: 13 (4 ULg)
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See detailPharmacological evaluation of BM-573, a dual thromboxane A2 receptor antagonist and thromboxane synthase inhibitor, as potential anti-metastatic agent
De Leval, X.; Dassesse, T.; Benoît, V. et al

Poster (2003, December)

Detailed reference viewed: 6 (0 ULg)