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Biomedical subjects

J Lelorier

Publications and source records attributed to J Lelorier.

At least 19 recordsLinked to original sources
PubMed2006

Assessment of Canadian provincial expenditures in depressed patients treated with venlafaxine XR versus SSRIs: the APEX Study.

OBJECTIVE: Empirical studies of antidepressant cost-effectiveness suggest that the use of venlafaxine may be no more costly than selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression. The objectives of this study were to identify patients' characteristics and factors associated with the choice of antidepressant and to assess differences in persistence, healthcare utilization and direct medical costs associated with venlafaxine and SSRIs pharmacotherapy. RESEARCH DESIGN AND METHODS: We examined demographic and clinical characteristics of patients (n = 17 144) who received both a diagnosis of depression and a prescription for venlafaxine or an SSRI between 1996 and 2004 using the Quebec health administrative databases. Logistic regression models were used to identify factors independently associated with the choice of antidepressant. Persistence to treatment and overall direct medical costs during 12 months after initiation of therapy were assessed using Cox proportional hazard and GLM models, respectively. RESULTS: Age, sex, provider specialty, and prior 12-month healthcare utilization significantly influenced initial antidepressant choice. Fewer venlafaxine-treated patients discontinued their initial therapy relative to SSRIs' (persistence to initial treatment: 38.4% vs. 29.4% and 24.4% vs. 15.8% at 6 and 12 months, respectively; p < 0.0001), and they were less likely to require treatment switching. Overall 12-month direct medical costs for SSRI- and venlafaxine-treated patients were Can$2759 and Can$2604, respectively. Patients treated with SSRIs had significantly higher expenditures in a univariate analysis (cost ratio: 1.06 [95% CI: 1.02, 1.10]). However, after controlling for potential confounding factors such as patients' characteristics, prior healthcare utilization, and comorbid conditions in multivariate analyses, the overall expenditures were similar in both groups (cost ratio: 1.03 [95% CI: 0.99, 1.07]). CONCLUSIONS: Direct medical costs were generally similar among patients with depression treated with venlafaxine and SSRIs. In a 'real world' setting, the higher acquisition cost of venlafaxine is offset by savings due to fewer hospitalizations and fewer outpatient medical visits. Differences in treatment persistence may also, in part, explain the observed differences in average direct medical costs between venlafaxine and SSRIs.

Adolescent↗
PubMed1984

Hypotension and arteriovenous shunting: effects of intravenous infusion of nitroprusside, nitroglycerin and phentolamine.

The effects of nitroprusside, nitroglycerin and phentolamine on cardiac dynamics and on the fraction of cardiac output shunted through systemic arteriovenous communications, which may explain disparate responses elicited by these systemic vasodilators upon venous return, have been studied in 15 nonanesthetized dogs. Cardiac dynamic parameters were measured by electromagnetic flow probe placed at the root of the aorta. Quantitative measurements of total systemic arteriovenous shunting were determined from the fraction of 9 mu radioactively labeled microspheres, injected into the left atrium, recovered in the pulmonary artery. To provide a common basis for comparison, the mean arterial pressure was lowered by 15-20% either with an intravenous infusion of nitroprusside, nitroglycerin or phentolamine. At the fifteenth minute of infusion, nitroprusside produced significant decrease in stroke volume index (23%) and left ventricular power and work (28% and 40%). Nitroglycerin decreased significantly stroke volume index (12%), cardiac index (9%) and left ventricular work (22%). Phentolamine significantly increased heart rate (72%) and left ventricular maximum acceleration (30%) while it decreased stroke volume index (41%), left ventricular power and work (19% and 55%). Total peripheral resistance was significantly affected only by infusion of phentolamine (-18%). Left ventricular maximum velocity, mean systolic ejection rate and maximum systolic flow did not change significantly under infusion of these systemic vasodilators. Under control conditions, total systemic shunting of cardiac output averaged 8.9-10% and was not modified by any of the vasodilators used. Arteriovenous O2 difference and oxygen consumption, corroborated these findings since they remained within normal limits before and after infusion of nitroprusside, nitroglycerin or phentolamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Cimetidine interaction with dipotassium clorazepate disposition in the anesthetized dog.

Cimetidine (CIM) was used as an interacting agent on the disposition in dogs of dipotassium clorazepate ( CZP ) and its main metabolite nordiazepam (ND) in order to study some of the factors contributing to pharmacokinetic interspecies variation of benzodiazepines in dogs and man. A 0.5 mg/kg of body weight intravenous (i.v.) bolus dose of CZP was administered to 12 anesthetized mongrel dogs, 6 of them receiving also, 30 min before, a 1 mg/kg i.v. bolus dose of CIM followed by a constant i.v. infusion (1 mg/kg/hr) of CIM. Plasma ND and CZP concentrations were measured as a function of time with an high-performance liquid chromatography method. Plasma levels of CZP declined mono- and biexponentially in 1 and 5 dogs, respectively, for each group of animals. No statistically significant difference was found between CZP pharmacokinetic parameters when the 2 groups of dogs were compared. However, a 37% decrease in ND beta half-life, t1/2 beta, when CZP was associated with CIM, was found to be statistically significant. The i.v. administration of pure ND in two dogs, has shown that ND declines biexponentially with a t1/2 beta similar to the one estimated after CZP dosing in control animals. The hepatic metabolism of ND was found to be flow-independent and restrictive. The data, along with previously reported CIM interactions, suggest that several factors, which would be species-dependent, must be responsible of CIM effect on other drugs.

Anesthesia↗
PubMed1983

High-performance liquid chromatography determination of dipotassium clorazepate and its major metabolite nordiazepam in plasma.

A rapid and sensitive high-performance liquid chromatographic method is described for the quantitative analysis of dipotassium clorazepate (CZP) and its major metabolite nordiazepam (ND) in fresh human and dog plasma. The method consists of two separate selective ND extractions from a plasma sample without and with conversion of all the CZP to ND. For quantitation, diazepam (DZP) is used as the internal standard. The chromatographic phase utilized in a reversed-phase Hibar EC-RT analytical column prepacked with LiChrosolv RP-18 with a solvent system consisting of acetonitrile-0.05 M sodium acetate buffer, pH 5.0 (45:55). The UV absorbance is monitored at 225 nm using a variable-wavelength detector. The mean assay coefficient of variation over a concentration range of 20-400 ng per ml of plasma is less than 3% for the within-day precision. Recoveries of ND, DZP and CZP (as ND) are essentially quantitative at all levels investigated. The calibration curves of ND are rectilinear (r2 = 0.99) from the lower limit of sensitivity (2 ng/ml) to at least 2000 ng/ml in plasma. Applicability of the method to CZP and ND disposition studies in the anaesthetized mongrel dog is illustrated. When the two separate selective nordiazepam extractions from plasma cannot be performed immediately after blood sampling, an extrapolation kinetic method is suggested for the estimation of CZP concentration. In all previous in vivo studies, CZP has been determined only with gas-liquid chromatographic methods.

Animals↗
PubMed1983

Tixocortol pivalate, a corticosteroid with no systemic glucocorticoid effect after oral, intrarectal, and intranasal application.

Tixocortol pivalate is a corticosteroid with topical anti-inflammatory activity equal to that of hydrocortisone. It was evaluated in a group of 18 normal subjects to determine whether it exerted any systemic glucocorticoid activity after single oral or intrarectal doses and after short-term dosing by the intranasal route. Effects of tixocortol pivalate were compared to those of oral dexamethasone and intrarectal betamethasone 21-phosphate. By the three routes, tixocortol pivalate does not induce any changes in plasma cortisol, leukocyte counts (neutrophils, lymphocytes, monocytes, eosinophils), blood glucose, or 24-hr urinary excretion of sodium and potassium, whereas there were changes after dexamethasone and betamethasone. Tixocortol pivalate, however, increased urinary free cortisol-like substances. It is concluded that tixocortol pivalate given for short periods by nonparenteral routes does not induce a measurable systemic glucocorticoid effect.

Administration, Intranasal↗
PubMed1983

Intravenous infusion of nitroprusside: effects upon cardiovascular dynamics and regional blood flow distribution in conscious dogs.

Intravenous infusion of nitroprusside (5 micrograms/kg/min) was carried out in conscious dogs over a 15-min period in order to describe changes in both central and peripheral vascular areas. Dogs were prepared with an electromagnetic flow probe positioned at the root of the aorta, and microspheres (9 microns) were used to measure regional blood flow distribution before and after 15 min of infusion. Controlled hypotension (-15 to -20 mmHg) was maintained throughout the infusion period and this hypotensive state was associated with a significant decrease in stroke volume (-16%), left ventricular power (-25%) and work (-40%) while cardiac index was not significantly affected. Those values were almost back to control levels 5 min following the end of infusion. Regional blood flow studies showed that at the fifteenth min of infusion, nitroprusside induced a significant decrease in blood perfusion to all areas of the myocardium (range -10% to -25%) while their local vascular resistances were not affected significantly. Blood perfusion to liver (hepatic artery), spleen and intestine was also modified significantly (-17%, -12% and -16%, respectively) while their vascular resistances remained close to control values. By the time measurements were made, blood flow to cerebral and renal tissues remained normal while their vascular resistances fell significantly (15% for brain and 20% for kidneys). For each organ studies, blood perfusion was uniform. These results indicate that nitroprusside elicits both central and peripheral hemodynamic changes and that reflex adjustments modify the vasodilator effect of the drug in most vascular beds that we have studied.

Animals↗
PubMed1982

Intravenous infusion of nitroglycerin: effects upon cardiovascular dynamics and regional blood flow distribution in conscious dogs.

We have studied both central and peripheral hemodynamic changes induced by infusion of nitroglycerin (55 micrograms/kg per minute) over a 15-min period in conscious dogs to clarify its mechanism of action. Dogs were prepared with an electromagnetic flow probe positioned at the root of the aorta, and microspheres (9 microns) were used to measure regional blood flow distribution before and after 15 min of infusion. Controlled hypotension (-15 to -20 mmHg (1 mmHg = 133.322 Pa)) was maintained throughout the infusion period and this hypotensive state was associated with a significant decrease in stroke volume (-30%), cardiac index (-20%), and left ventricular work (-43%). Regional blood flow studies showed that at the 15th min of infusion, nitroglycerin induced significant decrease in blood flow to all components of the myocardium (range -12 to -20%) while their vascular resistances were not affected significantly. Blood perfusion to liver (hepatic artery), spleen, and intestine was also modified significantly (-22, -18, and -16%, respectively) while their vascular resistances remained close to control values. By the time measurements were made, blood flow and vascular resistance of cerebral and renal tissues remained normal. For each organ studied, blood perfusion was uniform. These results indicate that nitroglycerin elicits both central and peripheral hemodynamic changes and that local reflex adjustments modify the vasodilator effect of the drug in most vascular beds that we have studied.

Animals↗
PubMed1982

The gastric antisecretory effects of clofibrate in the rat.

The object of this study was to explore the effect of clofibrate on gastric secretion. The volume and the total acid output of Shay-treated rats (pyloric ligation) was studied after intragastric, intraduodenal, intramuscular and intraperitoneal administration of clofibrate. The experimental model was a factorial (3 X 4) random block design. The treatment factor had 3 levels: water, oil and clofibrate. The route of administration factor had 4 levels: intragastric, intraduodenal, intraperitoneal and intramuscular. The data were analyzed by analysis of variance. Compared to the control group (water and oil) the intraduodenally and intraperitoneally administered clofibrate produced a statistically significant (p less than 0.001) reduction in the volume and total acid output. The intragastric and intramuscular groups did not show a statistically significant reduction on the gastric secretion. It is concluded that clofibrate acts systemically rather than locally to reduce gastric secretion.

Administration, Oral↗
PubMed1981

Effect of water deprivation and rehydration on gentamicin disposition in the rat.

To study the effect of dehydration on gentamicin (G) kinetics, a group of rats was deprived of water for 4 days and then received a single i.v. dose of 3 mg/kg of G. Compared to control rats, the plasma and tissue concentration of G in dehydrated rats were increased and the elimination rate of the drug decreased. Higher G concentrations were found in plasma, spleen, renal cortex and medulla. These changes in G disposition consisted in a decrease of 33 and 22% of the apparent volume of distribution of the peripheral and central compartments, respectively, and, furthermore, in a decrease of 40% in the G apparent total body clearance. Another group of rats, after a similar period of water deprivation and i.v. administration of 3 mg/kg of G, were rehydrated with water or received a solution of NaCl and dextrose followed by water during 24 hr. In plasma and most tissues, rehydration did accelerate G washout without clear differences between the two modes of rehydration. It is concluded that a dehydration state will increase plasma and tissue G accumulation and might increase the risk of renal or ototoxicity. Rehydration will partially prevent and reverse G concentration. In a clinical setting, this event could very well occur. G tissue concentration cannot be predicted by changes in G plasma elimination half-life. The calculation of total body clearance and volume of distribution are necessary to predict the occurrence and estimate the extent of this tissue concentration.

Animals↗
PubMed1980

High-pressure liquid chromatographic determination of lidocaine and its active deethylated metabolites.

A simple, specific, high-pressure liquid chromatographic method for lidocaine, and its active dealkylated metabolites, monoethylglycinexylidide (I) and glycinexylidide (II), is described. Recoveries were 94% for lidocaine, 98% for I, 77% for II, and 99% for the internal standard, ethylmethylglycinexylidide (III). The sensitivity of the assay is 0.04 microgram/ml. Coefficients of variation for day-to-day replicate analyses of lidocaine and the metabolites were < 7%.

Chromatography, High Pressure Liquid↗
PubMed1980

Effects of smoking and chronic hepatitis B on lidocaine and indocyanine green kinetics.

Kinetics of lidocaine (L) and indocyanine green (ICG), substances with a high hepatic extraction ratio, was studied in 9 normal subjects (4 smokers and 5 nonsmokers) and in 6 patients with chronic type B hepatitis without portal hypertension. L metabolism was studied in each subject after intravenous and oral administration. The data were used to calculate L systemic and oral clearances, L systemic bioavailability, and apparent hepatic blood flow. In smokers, L systemic bioavailability was decreased secondary to a marked increase in oral clearance, reflecting induction of drug-metabolizing activity. In patients with chronic hepatitis, L systemic and oral clearances were higher than in the normal. These findings indicate that hepatic handling of drugs with a high hepatic extraction ratio, such as L, might be enhanced in patients with chronic type B hepatitis. L disposition approach was validated in 5 patients by comparing results with those using the ICG clearance and extraction method at the time of hepatic vein catheterization. The L systemic bioavailability after oral administration is a reflection of first-pass clearance by the liver and might be a useful kinetic method for evaluating overall ability of the liver to remove drugs with high hepatic extraction ratios.

Administration, Oral↗
PubMed1977

GLC determination of lidocaine in human plasma.

A specific, sensitive, rapid, and reproducible analytical GLC method for lidocaine in human plasma, including pharmacokinetic parameters, is described. Aminopyrine is the internal standard. The method was used to study pharmacokinetics in four healthy volunteers following the administration of a lidocaine bolus at a dose of 1 mg/kg iv and in one patient with cardiac arrhythmias who had been given a 50-mg bolus followed by a prolonged intravenous infusion for 30 hr.

Aminopyrine↗
PubMed1977

Effect of norepinephrine on intramyocardial distribution of blood flow in normal and ischemic myocardium.

Using labelled microspheres, the effect of norepinephrine (NE) infusions (15 microgram and 30 microgram/min) on coronary blood flow and its intramyocardial distribution during ischemia was studied. The results reported here show that in the ischemic myocardium, the ratio of endocardial to epicardial flow was 0.67. This value became 1.0 in dogs receiving NE at a dose of 30 microgram/min. Since an adrenergic discharge is known to accompany angina in man, these data suggest that an imbalance between the endocardial and epicardial blood flow might not be present in this clinical condition.

Animals↗
PubMed1976

Acetylcholinesterase and responses to acetylcholine in the embryonic chicken heart.

Three and 4 day old embryonic chicken hearts were examined for their responsiveness to acetylcholine and presence of acetylcholinesterase (AChE) to determine the role of the enzyme in the cardiac effects of the transmitter. The effects of acetylcholine on rate and contractility of 3 day old hearts were indistinguishable from those on 4 day old hearts. The effects were readily blocked by atropine at both stages of development. In 3 day old hearts the responses to acetylcholine were not affected by the AChE inhibitor physostigmine but in 4 day old hearts they were considerably potentiated. The effect of acetylcholine on the rates of 4 day old hearts is of short duration (5 min or less). In 3 day old hearts it persists for a much longer time. Thus, the appearance of AChE in the embryonic heart of the chicken does not seem to modify the responsiveness of the cholinergic receptor to the transmitter.

Acetylcholine↗
PubMed1976

Effect of 6-hydroxydopamine on diet-induced hyperlipidemia and atherosclerosis in the rat.

The effect of 6-hydroxydopamine (6-OH-dopamine) and of a cholesterol rich diet on the plasma and aortic cholesterol of female rats were studied. Both the diet and the 6-OH-dopamine produced an important increase in plasmatic and aortic cholesterol. A synergistic effect of these two treatments was observed on the plasma but not on the aortic cholesterol. The mechanism by which 6-OH-dopamine produces hypercholesterolemia and a increase in aortic cholesterol remains to be explained.

Animals↗
PubMed1975

Effect of ouabain on the innervated and noninnervated embryonic chick heart.

Attempts to assess the importance of the role played by endogenous catecholamines in the positive inotropic response to ouabain have produced contradictory results. The sympathetic nervous system is not present in the 4-day-old chicken embryo heart but is fully developed after 7 days of embryonic life. This was confirmed by the fact 4-day-old hearts do not respond to tyramine and cocaine while the usual positive inotropic and chronotropic responses were observed when these drugs were administered to 7-day-old hearts. In spite of this difference the positive inotropic response to ouabain was virtually identical at these two stages of development.

Animals↗