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Biomedical subjects

J Blanchard

Publications and source records attributed to J Blanchard.

At least 145 records · Page 8Linked to original sources

Rate of expulsion of Trichuris trichiura with multiple and single dose regimens of albendazole.

The efficacy of multiple and single dose regimens of albendazole on Trichuris trichiura infection was evaluated by counting the number of worms expelled/day from two pair-matched groups of children, for nine days following therapy. The temporal patterns of worm expulsion were similar whether the children received a single 400 mg dose or two consecutive doses: no worms were passed before the second day, or after the sixth day, after intervention, and the maximum worm expulsion rate was attained on the fourth day. A second treatment six days after the first expelled no more worms. The results obtained here resemble those obtained previously with a three-day (600 mg) regimen of mebendazole in a study of heavily infected children. We conclude: that irrespective of dose, benzimidazole carbamates require the gut transit time plus 48 hours to immobilize T. trichiura; and that a single dose of albendazole is effective against light infections of T. trichiura but requires further evaluation with high intensity infections.

Albendazole↗

Comparison of the urinary metabolite profile of caffeine in young and elderly males.

The urinary metabolite profile of caffeine was compared in a group of seven healthy young men aged 18-29 years and in a group of five healthy elderly men aged 66-71 years. All subjects were given 5 mg/kg doses of caffeine as an aqueous oral solution or an intravenous infusion on two separate occasions in a randomized crossover design. Urine samples were collected for 24 h after dosing and analysed for caffeine and eleven of its metabolites by high-performance liquid chromatography. The effects of age, route of administration, and order of administration by route on the metabolite profile of caffeine were examined. The route of administration and the order of administration by the two routes were found not to influence the urinary metabolite pattern significantly. The urinary metabolite profile did not vary substantially with age except for the observation that significantly greater amounts of 1-methyluric acid, 7-methyluric acid and 1,7-dimethyluric acid were excreted by the elderly subjects.

Adult↗

Effect of pH on theophylline transfer across the everted rat jejunum.

The effect of pH on the cumulative transfer of theophylline across the everted rat jejunum in vitro was investigated. Intestinal integrity was assessed by light and scanning electron microscopy, while the biochemical viability of the intestine was evaluated using glucose transfer measurements. The initial (0-30 min) clearance of theophylline was directly proportional to the fraction un-ionized at pH 5.5, 7.4, 8.0, and 10.0. Plots of cumulative theophylline transfer versus time over 60 min were nonlinear, but could be subdivided into two linear segments of 30-min duration. Due to this nonlinearity, differences in theophylline transfer with pH were significant only over the first 30 min of the experiment. Intestinal tissue integrity and viability correlated with the time at which the clearance (slope) increased, while the magnitude of the increase in clearance was proportional to the degree of ionization of theophylline.

3-O-Methylglucose↗

[Bladder biopsy in the diagnosis of urogenital tuberculosis].

The authors report 5 cases of urogenital tuberculosis where examination of the urine failed to reveal any B.K. The diagnosis was suggested by the history of tuberculosis and the radiological appearance by intravenous pyelography. However, it was not possible to start an antituberculosis therapy in the absence of bacteriological proof. Forceps biopsy for histological examination provides an additional argument: the highly typical tuberculosis granuloma.

Adult↗

Relationship between urine flow rate and renal clearance of caffeine in man.

The renal clearance of caffeine was calculated following both oral and intravenous doses of 5 mg/kg caffeine in eight young and eight elderly, healthy human volunteers. There was a highly statistically significant positive correlation (P less than 0.001) between the renal clearance of both unbound (CLRu) and total (CLR) caffeine and the mean urine flow rate over the 24-hour period after dosing. Attempted correlations of CLRu and CLR with hydrogen ion concentration or creatinine clearance and of creatinine clearance with urine flow rate all proved to be statistically nonsignificant. It is suggested that the control of salt and fluid intake and other factors affecting urine flow rate may be a worthwhile endeavor in pharmacokinetic studies of drugs with properties similar to caffeine.

Adolescent↗

The absolute bioavailability of caffeine in man.

The absolute bioavailability of orally administered caffeine was investigated in 10 healthy adult male volunteers, aged 18.8 to 30.0 years. The subjects were administered a 5 mg/kg dose of caffeine as either an aqueous oral solution or an intravenous infusion, on separate occasions about 1 week apart, in a randomized crossover fashion. Plasma samples were collected over the 24-h period following each dose and assayed for their caffeine content using a high-performance liquid chromatographic technique. The oral absorption was very rapid, reaching a peak (Tp) plasma concentration after 29.8 +/- 8.1 min (mean +/- SEM). In addition, the variation in the maximum plasma concentration (Cmax) was low, 10.0 +/- 1.0 micrograms/ml. The absolute bioavailability was assessed by comparing the areas under the plasma concentration vs. time curves for the intravenous and oral doses of caffeine. The rapid absorption resulted in essentially complete bioavailability of the oral caffeine, F(%) = 108.3 +/- 3.6%. The caffeine plasma half-lives varied from 2.7 to 9.9 h, indicating substantial inter-subject variability in its elimination.

Administration, Oral↗

Comparative pharmacokinetics of caffeine in young and elderly men.

The pharmacokinetic behavior of caffeine was compared in a group of eight healthy young men aged 20.5 +/- 2.0 years (mean +/- SD), and in a group of eight healthy, elderly men aged 71.2 +/- 3.9 years. Each subject was given a 5 mg/kg dose of caffeine as either an aqueous oral solution or an intravenous infusion over 30 min using a randomized crossover design. Plasma and urine samples were collected for 24 hr following each dose and analyzed for caffeine content using high-performance liquid chromatography. The peak times (tmax), peak concentrations (Cmax), and the percentage of the peroral dose systemically available, F(%), were essentially identical in both age groups, indicating that caffeine was absorbed rapidly and completely after peroral administration. These results also indicated that the first-pass metabolism observed in rats following the peroral administration of caffeine does not occur in either human group studied here. The elimination of caffeine during its terminal disposition phase was log-linear. Several between-group comparisons of other pharmacokinetic parameters were made. Although the average elimination rate constant was greater in the elderly, the difference did not reach statistical significance, possibly because of the considerable intersubject variability in the elimination rate of caffeine, with half-lives ranging from 2.27 to 9.87 hr. The average apparent volume of distribution was significantly lower in the elderly subjects while the clearances were slightly, but not significantly, larger in the elderly subjects. It appears that most aspects of the pharmacokinetic behavior of caffeine are very similar in young and elderly men.

Adolescent↗

A possible method to control prolongations of bleeding time under antiplatelet therapy with ticlopidine.

The interactions of oral and i.v. administrations of corticosteroids with the effects of ticlopidine were studied, in a search for an antidote for possible excessive prolongations of bleeding time induced by antiaggregating agents. Indeed, the results show that an i.v. injection of methylprednisolone or an oral treatment with prednisolone counteract the prolongation of bleeding time but do not interfere with the inhibition of platelet aggregation brought about by ticlopidine. This could be ascribed to a vasoconstrictive effect of corticosteroids, possibly through reduction of vascular prostacyclin release. If this mode of action was confirmed, this useful finding would essentially apply to ticlopidine, but not to cyclooxygenase inhibitors such as aspirin which, by themselves, abolish prostacyclin production.

Adenosine Diphosphate↗

Protein binding of caffeine in young and elderly males.

The plasma protein binding of caffeine in young and elderly males was evaluated using an ultrafiltration technique. In spite of a significantly lower plasma albumin concentration in the elderly subjects the observed percent bound (approximately 35%) was essentially identical in both subject groups. The binding of caffeine to human plasma albumin (4.5% w/v) in vitro was also examined using ultracentrifugation and it was observed to be bound to the extent of 37.8%. In both the plasma and albumin binding studies the free fraction remained constant over the range of concentrations examined. Although there was no apparent correlation between the percent bound and the albumin concentration in the plasma of either subject group the close agreement between the degree of binding of caffeine to albumin and human plasma indicates that albumin is likely the major plasma binding protein for caffeine.

Adolescent↗

The effect of vitamin C on the pharmacokinetics of caffeine in elderly men.

The influence of vitamin C on the pharmacokinetics of caffeine was investigated in 10 elderly males, age 66 to 86 yr. Caffeine was administered intravenously on three different occasions over a 7-wk period: before vitamin C restriction, after approximately 4 wk of vitamin C restriction (15 mg dietary intake per day), and after 2 wk of vitamin C supplementation (500 mg orally, twice daily). Blood and urine samples were collected over a 48-h period after each caffeine administration. The plasma half-life, rate constant of elimination, apparent volume of distribution, total body clearance, renal clearance, and metabolic clearance of caffeine were determined. Simultaneous plasma, whole blood and leukocyte vitamin C concentrations were obtained. All of the average vitamin C concentrations monitored (plasma, whole blood, and leukocyte) changed significantly during the study, corresponding to the alterations in dietary vitamin C intake. Conversely, none of the caffeine pharmacokinetic parameters evaluated changed significantly during the study. The average metabolic clearance was approximately 77 (ml hr-1) kg-1 and the average half-life was approximately 4.6 h for all caffeine administrations. These results indicate that the elimination of caffeine in the elderly is not affected significantly by the concentrations of vitamin C achieved during this study.

Aged↗

Cardiovascular effects of caffeine in elderly men.

Ten healthy elderly male volunteers were given 4 mg/kg of caffeine by intravenous infusion on three separate occasions. This resulted in mean peak plasma concentrations of caffeine of 7.4 +/- 0.7 micrograms/ml. Immediately after each of the three caffeine infusions, the mean systolic blood pressures increased 14, 7, and 16 mm Hg, and the mean diastolic blood pressures increased 7, 4, and 7 mm Hg, respectively. Both the systolic and the diastolic blood pressures returned to preinfusion values within 4 hours. The QS2 index and the left ventricular ejection time (LVET) index increased after caffeine, probably as a result of the caffeine-induced increase in arterial blood pressure. The pre-ejection period (PEP), the PEP/LVET ratio, and the diastolic time remained unchanged. Caffeine, in doses equal to those contained in 2 to 3 cups of coffee, produces an increase in blood pressure but has no demonstrable positive inotropic effect in healthy elderly men.

Aged↗