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Biomedical subjects

Y Lacasse

Publications and source records attributed to Y Lacasse.

At least 55 records · Page 3Linked to original sources
PubMed1992

Effect of an acute dose of alcohol on the pharmacokinetics of oral nifedipine in humans.

Pharmacokinetic and pharmacodynamic interactions of alcohol and nifedipine were assessed in 10 healthy human volunteers. Doses of 20 mg (2 x 10-mg capsules) of nifedipine were administered with either 150 ml of orange juice or 75 ml of alcohol (94%) in 75 ml of orange juice according to a crossover randomized design. Plasma nifedipine levels were monitored for 16 hr after each dosing, along with pulse rate and blood pressure. The relative bioavailability of nifedipine, measured as AUC, was increased by 54% (533 vs 346 ng.hr/ml) after the dose of alcohol (P less than 0.0002). However, there were no significant differences between treatments in Cmax, tmax, or t1/2. Although there was no difference in the systolic and diastolic blood pressure and pulse rate between the two treatment groups, the time to reach peak heart rate was significantly faster in the group treated with alcohol (1.4 vs 2.2 hr). This study shows that ethanol increases the bioavailability of nifedipine and decreases the time for onset of increased heart rate.

Administration, Oral↗
PubMed1990

Multiple-dose propranolol administration does not influence the single dose pharmacokinetics of quinapril and its active metabolite (quinaprilat).

To evaluate the influence of multiple dose propranolol administration on the single dose pharmacokinetics of quinapril and its active metabolite, quinaprilat, a drug-drug interaction study was performed in ten healthy volunteers. Each subject received a single 20 mg quinapril oral dose on Days 1 and 16 of the study. Oral propranolol doses of 40 mg BID were initiated on Day 3, titrated gradually to 80 mg TID by Day 10, and continued at 80 mg TID through Day 17. Comparable mean quinapril pharmacokinetic parameter values as well as comparable mean quinaprilat pharmacokinetic parameter values determined following quinapril administered alone and following quinapril administered with propranolol, indicate that propranolol does not alter the single dose pharmacokinetics of quinapril or quinaprilat.

Adult↗
PubMed1981

Benzodiazepine overdosage: plasma concentrations and clinical outcome.

Plasma concentrations and their relation to clinical outcome were evaluated in 21 patients who reached emergency treatment facilities following acute overdosage with benzodiazepine derivatives. Diazepam was implicated in 18 of the 21 cases, with plasma diazepam levels ranging from 585-8,635 ng/ml. In four cases of overdosage with diazepam alone, patients were minimally sedated and were discharged within 24 h, despite diazepam doses as high as 750 mg and plasma levels as high as 4,792 ng/ml. However, concurrent ingestion of diazepam together with other central depressant drugs (such as ethanol, barbiturates, analgesics, or tricyclic antidepressants) produced serious intoxication in 5 of the remaining 14 patients, regardless of the diazepam dosage or plasma concentration. Thus the severity of poisoning following benzodiazepine overdosage is determined largely by co-ingestion of other central depressants rather than the amount of benzodiazepine ingested or its concentration in plasma.

Adolescent↗
PubMed1981

Presence of cadmium in the saliva of adult male workers.

Samples of mixed saliva were collected from 16 workers exposed to cadmium dusts and fumes and 19 unexposed co-workers. Samples of total blood and plasma were also obtained. Cadmium (Cd) was measured by flameless atomic absorption spectrometry. Cd was found in higher concentrations in saliva than in blood. The concentration of Cd in saliva was markedly elevated in exposed subjects; the difference was less important in blood. Smokers had more Cd in their blood than non-smokers, but this was not the case for saliva. In vitro studies measuring uptake of Cd by slices of rat submaxillary gland indicated that movement of the metal occurs passively.

Cadmium↗
PubMedDate not supplied

Pharmacokinetic characteristics of two different formulations of trimipramine determined with a new GLC method.

A sensitive and specific gas chromatographic method using a nitrogen detector for the measurement of trimipramine plasma concentrations is described. This method was used to determine the relative bioavailability and some pharmacokinetic parameters of two formulations, tablets and capsules, in healthy volunteers. It was concluded the tablet and capsule formulations were pharmacokinetically equivalent.

Adult↗
PubMedDate not supplied

Pharmacokinetic characteristics of ketoprofen suppositories.

The pharmacokinetic profile of ketoprofen suppositories following single and chronic (32 doses) administration to 12 healthy adult male volunteers was established. Each subject received a single rectal dose of 100 mg of ketoprofen on day 1, followed by one suppository of 100 mg b.i.d. for days 8--22, and finally one suppository on day 23. Plasma samples were analysed by gas-liquid chromatography. Following single doses, the mean maximum observed concentrations of ketoprofen in plasma (6.56 microgram ml-1) were achieved at 1.1 h; the mean elimination half-life was 1.78 h. The results indicate that ketoprofen is rapidly and reproducibly absorbed and eliminated from the suppository dose form.

Adult↗
PubMedDate not supplied

Pharmacokinetics of two lorazepam formulations, oral and sublingual, after multiple doses.

The pharmacokinetic profiles of a sublingual and a conventional oral lorazepam tablet formulation were established following chronic administration to twelve healthy male volunteers. Fitting a multi-dose equation based on a one-compartment model to the observed data, the average elimination half-lives for the sublingual and oral doses are estimated to be 11 and 8 h, respectively, while the corresponding absorption half-lives are 15 and 55 min; this confirms earlier reports that the sublingual formulation is more rapidly absorbed. The observed time to steady-state for both formulations was approximately 3 days, which agrees well with that predicted from previous single dosing studies. Although the sublingual formulation yields a higher average steady-state minimum plasma concentration than the oral formulation (41.6 versus 38.1 ng ml-1), the maximum lorazepam concentration achieved during steady state was approximately 83 ng ml-1 for both formulations. The average steady-state plasma concentration is estimated to be 63 ng ml-1, independent of the formulation used.

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetic and clinical parameters of zopiclone and trimipramine when administered simultaneously to volunteers.

Zopiclone is a new sedative showing a rapid onset of hypnotic effect and a relatively short duration of action. The goal of this study was to assess the kinetic parameters of zopiclone and its interaction with trimipramine when administered concomitantly. Ten normal subjects each received doses of zopiclone (7.5 mg), trimipramine (50 mg), and zopiclone (7.5 mg) + trimipramine (50 mg) orally at 7-day intervals. The absorption of zopiclone was rapid, the observed plasma peak concentration and 95 per cent of all absorption occurring within one hour. The average elimination half-life was 3.8 +/- 0.2 h. The volunteers reported a bitter taste at an average of 24 min after zopiclone administration at which time concentrations in saliva were approximately 50 ng ml-1. Trimipramine decreased the relative bioavailability determined for zopiclone by 13.7 per cent, while zopiclone decreased the relative bioavailability of trimipramine by an average of 26.6 per cent, although neither of these changes was statistically significant (p greater than 0.05); there were no substantial changes in other kinetic parameters. It is concluded that zopiclone presents advantages over some other sedative drugs as it is rapidly absorbed and eliminated. When zopiclone is administered with trimipramine, the decrease in the relative bioavailability of trimipramine may be clinically significant.

Adolescent↗
PubMedDate not supplied

The effect of administration of propranolol on the pharmacokinetics of isoxicam.

In order to examine a potential interaction between isoxicam and propranolol, single 200 mg doses of isoxicam were administered to ten healthy male volunteers before and during treatment with propranolol, gradually attaining a dose of 80 mg t.i.d. for 11 days. The pharmacokinetic profiles of the isoxicam plasma concentration/time data obtained over 96 h following the doses of isoxicam before and during propranolol administration were compared. No significant change was found in any of the pharmacokinetic parameters determined. These results suggest that propranolol has no effect on the metabolic disposition of isoxicam.

Adolescent↗
PubMedDate not supplied

The effect of administration of phenytoin on the pharmacokinetics of isoxicam.

This study was designed to determine whether the disposition of isoxicam is influenced by the coadministration of another acidic drug, highly bound to plasma proteins and extensively metabolized, i.e., phenytoin. Ten healthy volunteers received an oral dose of 200 mg of isoxicam prior to and following the oral administration of phenytoin (100 mg) twice a day for 10 days. Eleven blood samples were drawn during the period following each dose of isoxicam. The area under the isoxicam plasma concentration-time curve (AUC infinity) increased from 389 +/- 66 to 464 +/- 62 micrograms h ml-1 (+/- SEM) (p less than 0.05) after treatment with phenytoin. This increase was due to an increase in isoxicam bioavailability; the absorption rate constant for isoxicam increased correspondingly from 0.34 +/- 0.06 to 1.16 +/- 0.38 h-1 (p less than 0.05). Distribution and clearance of isoxicam were probably not affected as its half-life was not changed, its plasma peak concentration increased, and the time to reach this peak decreased. It is concluded that phenytoin increases the rate and extent of absorption of isoxicam.

Adult↗
PubMedDate not supplied

Influence of removal from occupational lead exposure on blood and saliva lead concentrations.

Samples of total blood and unstimulated mixed saliva were obtained from 5 male workers occupationally exposed to lead at various time intervals after removal from their work environment. Initial blood lead concentrations were elevated in all workers and then slowly decreased upon removal. Lead concentrations in saliva fell much more abruptly than those in blood, the saliva half-lives being estimated at 5-7 days. Temporary return to work in 2 workers resulted in relatively marked increases of salivary lead concentrations. These results suggest that salivary lead is closely related to recent lead exposure.

Environmental Exposure↗
PubMedDate not supplied

Prevalence of depressive symptoms and depression in patients with severe oxygen-dependent chronic obstructive pulmonary disease.

PURPOSE: To measure the prevalence rate of significant depressive symptoms and depression and examine their consequences on quality of life in patients with severe oxygen-dependent chronic obstructive pulmonary disease (COPD). METHODS: Between November 1997 and March 1998, the authors conducted a cross-sectional study among the COPD patients registered at the Quebec City area respiratory home care service. Depression and quality of life were assessed using the Geriatric Depression Scale and the Medical Outcome Survey--Short Form 36 (SF-36). RESULTS: 109 patients (63 men; mean age: 71) with severe COPD (median FEV1: 34%) were surveyed. Of them, 105 were on long-term oxygen therapy (LTOT), which had been introduced (median) 19 months earlier. Sixty-two patients (57%; 95% Cl: 47-66) demonstrated significant depressive symptoms; in addition, 20 patients (18%; Cl: 12-27) were severely depressed. Only 6% of those patients who met the criteria for depression were taking an antidepressant drug. We found significant and moderate correlations between the scores obtained from the Geriatric Depression Scale and 7 of the 8 domains of the SF-36. CONCLUSION: Significant depressive symptoms and depression are highly prevalent in patients with severe COPD on LTOT. There is strong evidence that depression is under-recognized and under-treated in this group of patients.

Aged↗