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S Perreault

Publications and source records attributed to S Perreault.

18 recordsLinked to original sources
PubMed2005

Persistence and determinants of statin therapy among middle-aged patients for primary and secondary prevention.

AIMS: Statins have been shown to significantly reduce morbidity and mortality in patients with coronary artery disease (CAD), and also in patients with dyslipidaemia when statins are taken regularly. Middle-aged patients have the highest level of forecasting benefit and little is known about persistence rate of these therapies in a real-life setting. The objective was to evaluate the persistence rate of middle-aged patients initiating a statin therapy and its relation with several determinants for primary and secondary prevention. METHODS: A cohort was reconstructed using the RAMQ databases. All patients aged 50-64 years-old who received at least one statin prescription between 1 January, 1998 and 31 December, 2000 for a new intention of treatment for dyslipidaemia were included in the cohort and followed up until 30 June, 2001. The date of the first prescription of statin was defined as the index date. There were 4316 patients in the secondary prevention (CAD diagnosis) and 13,642 patients in primary prevention cohort. The cumulative persistence rate was estimated using Kaplan-Meier, and Cox regression models were used to estimate the hazard ratio of ceasing statins. RESULTS: We found that persistence with statins had fallen to 71% after 6 months of treatment, and had declined to 45% after 3 years in the secondary prevention cohort; the corresponding figures were 65% and 35% in the primary prevention cohort. Our results suggest that patients with dyslipidaemia in primary prevention compared with those in secondary prevention (HR: 1.18; 1.11-1.25) are less likely to be persistent. Patients with other cardiovascular risk factors such as age (HR: 0.99; 0.98-0.99), diabetes (HR: 0.84; 0.79-0.90), hypertension (HR: 0.76; 0.72-0.80) were most likely to be persistent with statins. We observed lower persistence in patients who have used the greatest number of pharmacies and prescribing physicians. CONCLUSION: This analysis indicates that barriers to persistence occur early in the therapeutic course. Overall persistence with statins is low, and particularly among patients with few other cardiovascular risk factors.

Cohort Studies↗
PubMed2001

Pharmacokinetics of morphine and its glucuronidated metabolites in burn injuries.

OBJECTIVE: To investigate the effects of major thermal burn injury and continuous intravenous morphine infusion on the disposition of morphine and its glucuronidated metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) once a week for three weeks. CASE SUMMARIES: Five patients with major first-, second-, or third-degree burn injuries received long-term intravenous morphine infusion. The required dose varied greatly (from 4 to 39.5 mg/h). The steady-state concentrations of morphine, M3G, and M6G ranged from 20 to 452, 29 to 3436, and 20 to 1240 mumol/L, respectively. The systemic clearance (Cls) of morphine ranged from 14.8 to 40.3 mL/min/kg and did not change over time. The ratios of M6G and M3G to morphine were not affected by dose, even with the wide variation of intravenous dosage. Morphine kinetics appeared to be first-order. Mean recovery of morphine, M3G, and M6G in urine was 1.7 +/- 1.0%, 42.0 +/- 16.8%, and 11.8 +/- 3.2%, respectively, and renal clearance ranged from 8 to 64, 26 to 325, and 59 to 589 mL/min, respectively. Mean pain intensity ratings at rest remained low and stable (0.7 +/- 0.9 on day 7, 0.4 +/- 0.3 on day 14, 0 +/- 0 on day 21). DISCUSSION: To our knowledge, this is the first published report describing morphine, M3G, and M6G disposition in patients with major thermal burn injury. The Cls of morphine is similar to that observed in other patient populations and healthy subjects, suggesting that the presence of major burn injuries or a continuous morphine infusion over a three-week period may not contribute significantly to the variability among individuals. In these cases, the renal clearance of morphine and its glucuronides was within the range of values reported for other populations of patients and healthy subjects. Recovery of morphine and its glucuronides in urine was also similar to that in healthy individuals. CONCLUSIONS: These cases suggest that the effects of major burn injuries and of long-term intravenous infusion of morphine did not seem to modify morphine, M3G, and M6G disposition. Among patients with burn injuries, the severity of burns of duration of administration are not a cause of nonlinear kinetic of morphine or of morphine resistance. The morphine infusion rate was substantially variable and not directly related to its clearance, suggesting that monitoring of morphine should be focused on the clinical response.

Adult↗
PubMed2000

Savings in direct medical costs from the use of tobramycin solution for inhalation in patients with cystic fibrosis.

OBJECTIVE: Two identical 24-week, double-blind, placebo-controlled trials of tobramycin solution for inhalation (TOBI [PathoGenesis Corporation, Seattle, Washington]) in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection were conducted in the United States. The aim of the present study was to extrapolate the US trial data to a Canadian setting, using Canadian costs to estimate the savings in direct medical costs that might result from use of a similar 24-week TOBI regimen versus usual care in 2 Canadian provinces. BACKGROUND: Cystic fibrosis is a genetic disease in which persistent respiratory infection, usually due to P. aeruginosa infection, is the major cause of morbidity and mortality. METHODS: The US trials demonstrated that TOBI produced significant improvements in pulmonary function test results, reduced sputum levels of P. aeruginosa, and resulted in a 26% reduction in the probability of hospitalization (95% CI, 2%-43% vs placebo in the clinical trials). Individual patient data from the US trials were used to calculate the mean number of days in hospital as well as the mean number of days of home intravenous or oral antibiotic therapy. To adjust for Canadian pricing, pertinent economic data were obtained from Statistics Canada and the Ontario and Quebec health ministries. Demographic and baseline data were obtained from health surveys conducted by the Canadian Cystic Fibrosis Foundation. RESULTS: Economic analysis showed that the use of TOBI for 24 weeks would result in estimated mean per-patient savings in direct medical costs (in Canadian dollars) of $4055 in Ontario and $4916 in Quebec, which would substantially offset the Canadian acquisition price of $8602 for the same 24-week period. CONCLUSIONS: Assuming that the percentage of reduction in hospital days observed in the US trials would also occur in the Canadian clinical setting, use of TOBI would reduce the use of health care services, particularly hospital days, and lead to substantial savings in direct medical costs that would offset its acquisition price. Whether this reduction actually occurs after TOBI enters the Canadian market is a subject for future investigation.

Administration, Inhalation↗
PubMed2000

Efficacy and cost of HMG-CoA reductase inhibitors in the treatment of patients with primary hyperlipidemia.

BACKGROUND: Screening for hyperlipidemia is a substantial cost burden, as is its treatment. The choice of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and the dose level may have significant implications for both efficient and cost effective therapy. OBJECTIVE: To compare the efficiency and cost of statins. MATERIALS AND METHODS: A meta-analysis was conducted of randomized, controlled trials of monotherapy with fixed doses of statins published in the literature until June 1998. Two authors independently extracted data from 49 trials comprising 14,130 patients. The percentage reduction (95% confidence intervals) of low density lipoprotein (LDL) cholesterol levels was calculated using a random-effects model. Cost efficiency was defined as the percentage decline of LDL cholesterol per dollar of drug cost. RESULTS: The population evaluated had a mean baseline LDL cholesterol concentration of 5.31 mmol/L, a mean age of 53.5 years and a mean 59% proportion of males. In reducing LDL cholesterol concentrations to less than 25% of the baseline concentration, a significantly higher cost efficiency was achieved with simvastatin 2.5 mg (-53.3%/dollar). By targeting a reduction between 25% and 29%, significantly higher cost efficiencies were found with simvastatin 5 mg (-28.9%/dollar), cerivastatin 0.2 mg (-23.8%/dollar) and fluvastatin 40 mg (-23.3%/dollar). For reductions in LDL cholesterol concentrations of 30% to 34%, statistically higher cost efficiencies were achieved with simvastatin 20 mg (-15.0%/dollar) and pravastatin 40 mg (-14. 4%/dollar). Finally, atorvastatin 10 mg yielded a value of -22. 9%/dollar for a 36% reduction in LDL cholesterol concentration. CONCLUSIONS: At current prices of the various doses of statins, the cost efficiency of standard and more aggressive therapies varies substantially. In the context of health care budgets, targeting at-risk patients and using statins judiciously should facilitate the efforts of clinicians and patients to reduce lipid profiles optimally and decrease the cost burden.

Cost-Benefit Analysis↗
PubMed1999

Impact of treating hyperlipidemia or hypertension to reduce the risk of death from coronary artery disease.

OBJECTIVE: To compare the prevalence of modifiable risk factors for cardiovascular disease among hypertensive and nonhypertensive adults and to estimate the effect of treating hyperlipidemia or hypertension to reduce the risk of death from coronary artery disease. METHODS: The authors evaluated a sample of 7814 subjects aged 35-74 years free of clinical cardiovascular disease from the Canadian Heart Health Surveys to estimate the prevalence of cardiovascular risk factors. They identified hyperlipidemic subjects (ratio of total cholesterol to high-density lipoprotein cholesterol [total-C/HDL-C] 6.0 [corrected] or more for men and 5.0 [corrected] or more for women) and hypertensive subjects (systolic or diastolic blood pressure 160/90 mm Hg or greater, or receiving pharmacologic or nonpharmacologic treatment). A life expectancy model was used to estimate the rate of death from coronary artery disease following specific treatments. RESULTS: An elevated total-C/HDL-C ratio was significantly more common among hypertensive than nonhypertensive men aged 35-64 (rate ratio [RR] 1.56 for age 35-54, 1.28 for age 55-64) and among hypertensive than nonhypertensive women of all ages (RR 2.73 for age 35-54, 1.58 for age 55-64, 1.31 for age 65-74). Obesity and a sedentary lifestyle were also more common among hypertensive than among nonhypertensive subjects. According to the model, more deaths from coronary artery disease could be prevented among subjects with treated but uncontrolled hypertension by modifying lipids rather than by further reducing blood pressure for men aged 35-54 (reduction of 50 v. 29 deaths per 100,000) and 55-64 (reduction of 171 v. 104 deaths per 100,000) and for women aged 35-54 (reduction of 44 v. 39 deaths per 100,000). Starting antihypertensive therapy in subjects aged 35-74 with untreated hypertension would achieve a greater net reduction in deaths from coronary artery disease than would lipid lowering. Nonetheless, the benefits of lipid therapy were substantial: lipid intervention among hypertensive subjects aged 35-74 represented 36% of the total benefits of treating hyperlipidemia in the total hyperlipidemic population. INTERPRETATION: The clustering of hyperlipidemia and the potential benefits of treatment among hypertensive adults demonstrate the need for screening and treating other cardiovascular risk factors beyond simply controlling blood pressure.

Adult↗
PubMed1998

Treating hyperlipidemia for the primary prevention of coronary disease. Are higher dosages of lovastatin cost-effective?

OBJECTIVE: To compare the average and marginal life-time cost-effectiveness of increasing dosages of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin, for the primary prevention of coronary heart disease (CHD). METHODS: We estimated the lifelong costs and benefits of the modification of lipid levels achieved with lovastatin based on published studies and a validated CHD prevention computer model. Patients were middle-aged men and women without CHD, with mean total serum cholesterol levels of 6.67, 7.84, and 9.90 mmol/L (258, 303, and 383 mg/dL), and high-density lipoprotein cholesterol levels of 1.19 mmol/L (46 mg/dL), as described in clinical trials. We estimated the cost per year of life saved for dosages of lovastatin ranging from 20 to 80 mg/d that reduced the total cholesterol level between 17% and 34%, and increased high-density lipoprotein cholesterol level between 4% and 13%. RESULTS: After discounting benefits and costs by 5% annually, the average cost-effectiveness of lovastatin, 20 mg/d, ranged from $11,040 to $52,463 for men and women. The marginal cost-effectiveness of 40 mg/d vs 20 mg/d remained in this range ($25,711 to $60,778) only for persons with baseline total cholesterol levels of 7.84 mmol/L (303 mg/dL) or higher. However, the marginal cost-effectiveness of lovastatin, 80 mg/d vs 40 mg/d, was prohibitively expensive ($99,233 to $716,433 per year of life saved) for men and women, irrespective of the baseline total cholesterol level. CONCLUSIONS: Assuming that $50,000 per year of life saved is an acceptable cost-effectiveness ratio, treatment with lovastatin at a dosage of 20 mg/d is cost-effective for middle-aged men and women with baseline total cholesterol levels of 6.67 mmol/L (258 mg/dL) or higher. At current drug prices, treatment with 40 mg/d is also cost-effective for total cholesterol levels of 7.84 mmol/L (303 mg/dL) or higher. However, treatment with 80 mg/d is not cost-effective for primary prevention of CHD.

Anticholesteremic Agents↗
PubMed1998

Smoking cigarettes is associated with increased sperm disomy in teenage men.

OBJECTIVE: To determine whether moderate cigarette smoking and alcohol consumption in teenage men is associated with increases in disomic sperm and detectable changes in semen quality. DESIGN: Cohort study. SETTING: Military recruiting station, Teplice, Czech Republic. PATIENT(S): Ten current smokers (20 cigarettes per day for at least 2 years, exposure confirmed by urine cotinine) who also consumed alcohol and 15 nonsmokers. All patients were exactly 18 years old, healthy, and of unproven fertility. MAIN OUTCOME MEASURE(S): Sperm aneuploidy by multicolor fluorescence in situ hybridization for chromosomes 8, X, and Y; conventional semen analyses; computer-aided sperm analysis for motility; and sperm chromatin structure analysis. RESULTS: Smokers showed elevated frequencies of sperm aneuploidy (Y disomy, P <0.001; aggregate of X, Y, and 8 disomies, P <0.01); reduced linearity of sperm motion (P <0.05); and more "round-headed" sperm (P <0.01). Smokers' semen contained fewer sperm (P <0.001) and fewer motile sperm (P <0.02), which was attributable, in part, to shorter abstinence intervals among smokers (P <0.02). CONCLUSION(S): Cigarette smoking among teenagers was associated with increases in disomic sperm and a diminution in specific aspects of semen quality. Such defects may affect male fertility and may increase future chances of fathering offspring with aneuploidy syndromes.

Adolescent↗
PubMed1998

Efficacy and costs of patient-controlled analgesia versus regularly administered intramuscular opioid therapy.

BACKGROUND: Many studies have shown the efficacy of patient-controlled analgesia (PCA). However, it is not clear whether PCA has clinical or economic benefits in addition to efficient analgesia. The current study was designed to evaluate these issues by comparing PCA with regularly administered intramuscular injections of opioids after hysterectomy. METHODS: This prospective study included 126 patients who underwent abdominal hysterectomy and were randomly assigned to receive PCA or regularly timed intramuscular injections of morphine during a period of 48 h. Doses were adjusted to provide satisfactory analgesia in both treatment groups. Pain at rest and with movement, functional recovery, drug side effects, and patient satisfaction were measured using rating scales and questionnaires. The costs of PCA and intramuscular therapy were calculated based on personnel time and drug and material requirements. RESULTS: Comparable analgesia was observed with the two treatment methods, with no significant differences in the incidence of side effects or patient satisfaction. The medication dosage had to be adjusted significantly more frequently in the intramuscular group than in the PCA patients. The PCA did not favor a faster recuperation time compared with intramuscular therapy in terms of times to ambulation, resumption of liquid and solid diet, passage of bowel gas, or hospital discharge. The results of the economic evaluation, which used a cost-minimization model and sensitivity analyses, showed that PCA was more costly than regular intramuscular injections despite the fact that no costs for the pump were included in the analyses. Cost differences in nursing time favoring PCA were offset by drug and material costs associated with this type of treatment. CONCLUSIONS: Compared with regularly scheduled intramuscular dosing, PCA is more costly and does not have clinical advantages for pain management after hysterectomy. Because of the comparable outcomes, the general use of PCA in similar patients should be questioned.

Analgesia↗
PubMed1997

A head-to-head comparison of the cost effectiveness of HMG-CoA reductase inhibitors and fibrates in different types of primary hyperlipidemia.

The objective of this study was to compare the lifetime cost-effectiveness of HMG-CoA reductase inhibitors and fibrates for the treatment of hyperlipidemia. Estimates of lipid modification achieved due to drug therapy were based on published head-to-head comparisons of specific HMG-CoA reductase inhibitors and fibrates in randomized, double-blind studies. We used a validated coronary heart disease (CHD) prevention computer model to estimate the costs and benefits of lifelong lipid modification. The patients were middle-aged men and women who were free of CHD, with either primary type IIa or IIb hyperlipidemia. The intervention used were specific HMG-CoA reductase inhibitors and fibrates at several dosages, which reduced total cholesterol 11-34% and increased high-density lipoprotein cholesterol 1-29%. The main outcome measure was the cost per year of life saved after discounting benefits and costs by 5% annually. The lifetime cost effectiveness of HMG-CoA reductase inhibitors (fluvastatin, lovastatin, pravastatin, simvastatin) and fibrates (bezafibrate, fenofibrate, gemfibrozil) for the treatment of primary hyperlipidemia varied according to patient population, the effectiveness of each drug in modifying lipid levels, and the price of each drug. The estimates of cost per year of life saved for HMG-CoA reductase inhibitors range from $19,886 to $73,632, and $16,955 to $59,488 for fibrates according to gender and type of primary hyperlipidemia. Fluvastatin 20 mg/day was significantly more cost effective than gemfibrozil 1200 mg/day for male patients with type IIa hyperlipidemia. Simvastatin 17.3 mg/day or 20 mg/day yielded similar cost-effectiveness ratios compared with fibrates among type II hyperlipidemic patients. However, micronized fenofibrate was more cost effective than simvastatin 20 mg/day among type IIb patients. The cost effectiveness of lipid therapy varies widely and can be maximized by selecting specific drugs for specific lipid abnormalities.

Bezafibrate↗
PubMed1995

Influence of hypoxia and hypercapnia on the kinetics and hypokaliaemic effect of salbutamol in the rabbit.

1. The aims were to document the influence of moderate hypoxia or hypercapnia on salbutamol kinetics and its hypokaliaemic effect, following its administration through the intravenous (60 micrograms/kg), intratracheal (60 micrograms/kg), and oral (2400 micrograms/kg) routes (n = 5). In control animals, PaO2 was around 85 mmHg and PaCO2 20 mmHg; in hypoxic animals PaO2 was around 40 mmHg and in the hypercapnic rabbit PaCO2 was 50 mmHg. 2. Following the intravenous administration of salbutamol, the apparent volume of distribution increased two-fold (p < 0.05) in animals with hypoxia and hypercapnia. Consequently, its half life was enhanced (p < 0.05). Given via the trachea, salbutamol bioavailability was decreased by hypoxia. 3. When salbutamol was given orally, hypoxia or hypercapnia increased the area under salbutamol plasma concentration as a function of time (p < 0.05). 4. In control animals, the salbutamol hypokaliaemic effect was greater when administered orally than through the other routes. Compared with control animals, the experimental conditions reduced the hypokaliaemic effect of salbutamol only when given orally. 5. It is concluded that salbutamol kinetics and dynamics can be altered by hypoxia and hypercapnia.

Administration, Oral↗
PubMed1994

Influence of chronic hypoxia on salbutamol tissular concentrations and on respiratory resistance in anesthetized rabbits.

Salbutamol is a potent beta 2-adrenoceptor agonist given to patients with bronchial asthma who are frequently hypoxemic. The aims of this study were to document the influence of chronic hypoxia on salbutamol tissue concentrations and on salbutamol effect on total respiratory resistance. To this purpose, salbutamol (60 micrograms/kg) was administered intravenously to four groups of six rabbits exposed to four experimental conditions: (1) control rabbits breathing air, (2) histamine-induced bronchoconstriction in rabbits breathing air, (3) animals with chronic hypoxia, (4) histamine-induced bronchoconstriction in animals with chronic hypoxia. The area under salbutamol plasma concentration time curve (0 to 45 min) was not affected by these experimental conditions. Compared with control rabbits breathing air, following histamine-induced bronchoconstriction, salbutamol concentrations rose by 40 to 50% in lung and heart (p < 0.05). Hypoxia did not affect salbutamol distribution in these organs; however, in hypoxic animals, histamine-induced bronchoconstriction increased salbutamol concentrations only in the heart (p < 0.05), without affecting those in the lung. Compared with rabbits breathing air and with histamine-induced bronchoconstriction, the effect of salbutamol was reduced in rabbits under chronic hypoxia and histamine-induced bronchoconstriction (p < 0.05). We conclude that chronic hypoxia reduces salbutamol effect on pulmonary resistance, possibly by decreasing salbutamol lung concentrations.

Airway Resistance↗
PubMed1993

The effect of flumazenil on midazolam-induced depression of the ventilatory response to hypoxia during isohypercarbia.

BACKGROUND: While flumazenil reverses benzodiazepine-induced sedation, its ability to antagonize the ventilatory depressant effects of benzodiazepines has not been fully established. A randomized, double-blind study was conducted to determine whether flumazenil effectively reverses midazolam-induced depression of the hypoxic ventilatory response. METHODS: Twelve healthy male volunteers received intravenous midazolam 0.12 +/- 0.01 mg.kg-1 followed by either flumazenil 1.0 mg or placebo. Hypoxic ventilatory response was measured using an isocapnic rebreathing technique: as Spo2 decreased to 70% VE and tidal volume were continuously recorded. Hypoxic response determinations were performed before and after midazolam, as well as 3, 30, 60, 120, and 180 min after flumazenil or placebo. RESULTS: After midazolam, the slope of the hypoxic ventilatory response curve (VE vs. SpO2) decreased to 0.59 +/- 0.05 (means +/- SE) times its premidazolam baseline; likewise, at Spo2 = 90%, minute ventilation (VE90) and tidal volume (TV90) decreased to 0.70 +/- 0.04 and 0.62 +/- 0.03 times baseline, respectively. Three minutes after flumazenil, the slope increased to 1.10 +/- 0.13 times baseline (P < 0.05 vs. postmidazolam), while following placebo, it was only 0.81 +/- 0.09 times baseline (P = NS vs. postmidazolam, P < 0.05 between treatments). VE90 and TV90, after flumazenil, increased to 1.45 +/- 0.15 and 1.27 +/- 0.09 times baseline, respectively (P < 0.05 vs. postmidazolam); these increases were significantly greater than the corresponding changes observed after placebo (P < 0.05 between treatments). CONCLUSIONS: It was concluded that, after sedation with midazolam, flumazenil causes a greater increase in hypoxic ventilatory response during isohypercarbic conditions than does placebo, and may, therefore, be useful in the treatment of midazolam-induced ventilatory depression.

Adult↗
PubMed1992

Salbutamol disposition and dynamics in conscious rabbits: influence of the route of administration and of the dose.

This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 micrograms/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 micrograms/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 micrograms/kg), total plasma clearance was 82 +/- 5 ml/min per kg, apparent volume of distribution was 5.0 +/- 0.5 l/kg, and terminal half-life was 41 +/- 2 min. Similar values were estimated when 120 micrograms/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80 +/- 0.19, 0.48 +/- 0.22, and 0.78 +/- 0.46 mmol/l, and for the second group, maximal decrement was 1.31 +/- 0.37, 0.70 +/- 0.24, and 0.84 +/- 0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentrations. The hypokaliemic effect was dependent upon the route, e.g., po > it > iv.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Effect of salbutamol on gastroesophageal reflux in healthy volunteers and patients with asthma.

The aim of this work was to establish whether beta-adrenergic agonists promote or increase gastroesophageal reflux in patients with asthma. Ten healthy individuals and eight patients with asthma were studied on 2 different days. One day they received a placebo, and the other day they received 4 mg of salbutamol by mouth. Complete measurements of esophageal manometry were performed before and every 30 minutes for 210 minutes after the administration of the drugs. Esophageal pH was measured continuously for the duration of the experiment. The results demonstrate that (1) salbutamol had no effect on the lower esophageal sphincter pressure gradient, the peak esophageal contraction pressure, or the number and duration of reflux episodes in patients with asthma and normal individuals, and (2) patients with asthma have a resting lower esophageal sphincter pressure higher than healthy subjects. We conclude that the administration of salbutamol does not affect esophageal function.

Adolescent↗
PubMed1989

Analysis of albuterol in human plasma based on immunoaffinity chromatographic clean-up combined with high-performance liquid chromatography with fluorimetric detection.

A method combining immunoaffinity chromatography with high-performance liquid chromatography was developed for the determination of albuterol in human plasma. The immunoaffinity chromatography, based on the specific interaction of albuterol with the immobilized antibody raised against it, was used as a clean-up step. Albuterol eluted from this immunochemical solid-phase clean-up step was analysed by reversed-phase high-performance liquid chromatography with fluorimetric detection. The performance of the assay was validated on six normal volunteers after a 4-mg oral dose of albuterol, which gave a peak plasma concentration in the range 6.67-15.31 ng/ml at 3-4 h after the dose. Plasma levels (0.79-1.56 ng/ml) of albuterol could be detected up to 24 h after the dose.

Albuterol↗
PubMed1980

Inhibition of fertilization in the hamster by sodium aurothiomalate, a hyaluronidase inhibitor.

Sodium aurothiomalate, a low molecular weight inhibitor of hyaluronidase, blocked in-vitro fertilization in hamsters at the level of the zona pellucida: concentrations of 25-250 micrograms inhibitor/ml prevented fertilization of cumulus-intact and cumulus-denuded eggs. Fertilization of zona-free ova was not affected. In-vivo fertilization was also reduced (from 100% controls to 37.5%) by 10 mg inhibitor/ml added to an epididymal sperm suspension before artificial insemination into the uterus. These findings suggest that hyaluronidase may play a role in zona penetration or that sodium aurothiomalate blocks sperm penetration of the zona by inhibiting an enzyme(s) other than hyaluronidase.

Animals↗
PubMedDate not supplied

Hepatic and extrahepatic metabolism of salbutamol in anesthetized rabbits.

Orally administered salbutamol undergoes an extensive first-pass effect. This study investigated the roles of the intestine (INT), liver (HEP), and lung (LUN) in salbutamol extraction. Salbutamol was administered to five groups of anesthetized rabbits by the following routes: intraduodenal (ID) (800 micrograms/kg), intraportal (IP), (60 micrograms/kg), intrajugular (IV) (60 micrograms/kg), endotracheal (ET) (60 micrograms/kg), and intraarterial (IA) (60 micrograms/kg). Multiple blood samples were drawn and the areas under salbutamol plasma concentrations-time curves (AUCs) were calculated. Since IA salbutamol administration generated 100% bioavailability (F), AUCIA was used as a reference for comparison. Salbutamol F values for the ID, IP, IV, and ET routes were 0.013, 0.15, 0.53, and 0.53, respectively. The ratio of the AUC of salbutamol administered before the organ (ID, IP, IV, or ET) to the AUC estimated when given after the organ (IP, IV, and IA) allowed assessment of the extraction ratio (E) of INT, HEP, and LUN, respectively. EINT was 0.92, EHEP was 0.71, and ELUN was 0.47. The mean ratio of the AUC of the metabolite (AUCM) over the AUC of the parent compound was 704 +/- 77 for the ID, compared with 83 +/- 12 for the IP, 11 +/- 1 for the IV, 1.7 +/- 0.3 for the ET routes, and 4 +/- 1 for the IA routes. On the other hand, when the AUCM was normalized by the dose, this ratio was INT = HEP > LUN, suggesting that the ability of INT to conjugate salbutamol is not very important.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗