摘要:

Eighty-six Mexican young healthy volunteers received a 500-mg oral sulfamethazine dose. Urine was collected 0–6 h after medication and acetylated, and unchanged sulfamethazine were determined by the Bratton-Marshall method. The frequency distribution of acetylated/unchanged sulfamethazine, determined by probit analysis, appeared to be trimodal, allowing the discrimination of three acetylator phenotypes. The frequencies of rapid, intermediate, and slow acetylators were 28%, 42%, and 30% respectively, being consistent with the Hardy-Weinberg law.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The multiple-dose pharmacokinetics and safety of a new potential antidementia compound, CL 275,838, were examined in two randomized, double-blind, parallel-group, placebo-controlled studies. The Alzheimer Disease Assessment Scale (ADAS) was employed to preliminarily assess the patients' cognitive and the behavioral profiles. In the first study, nine patients with Alzheimer type or vascular dementia were treated for 2 weeks with daily doses of 50 mg. In the second study, nine other patients, selected with the same inclusion/exclusion criteria and treated following the same experimental design, were given 100 mg day−1CL 275,838. At the lower dose, no side effects were detected; in the 100-mgday−1study, mild drowsiness (one patient) and moderate agitation (two patients) were observed. Laboratory tests showed no changes in either study, apart from a slight, transient increase in serum bilirubin in one patient given 100 mg. At the dose of 50 mg, no patients showed any modification on the ADAS, whereas three patients given 100 mg showed some improvement. During the 2 weeks of oral dosing, predose plasma concentrations of the parent compounds and its metabolites II and IV increased but not in proportion to the dose, although at both doses, accumulation was essentially complete within 10 days. At 50 mg, the mean steady-state Cmaxand Cssof the parent compound were similar to those reached in young males after a comparable regimen. Mean steady-state metabolite-to-parent drug ratios were higher in patients than in healthy individuals, although there was wide variation in our patient group. Mean washoutt,1/2of the parent compound (34 h) and its metabolites II (37 h) and IV (41 h) were longer than in young men and were similar in all cases to those observed after single doses in healthy elderly subjects. After 100 mg, mean Cmaxand Cssof the unchanged compound rose more than proportionally and the apparentt1/2tended to rise, compared with the lower dose. Mean steady-state oral clearance decreased, changing the metabolite-to-parent drug ratios, suggesting nonlinear kinetics after several relatively high oral doses. This might explain why the higher dose was less well tolerated.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We investigated the effect of activated charcoal on rifampicin disposition in six healthy subjects. On three occasions (control, phases II and III, separated by 1 week), each subject received 600 mg of rifampicin with 350 ml of water. On the second and third occasions (phases II and III), each subject received in addition to 600 mg of rifampicin and 7.5 and 15 g of activated charcoal, respectively, in 350 ml of water as charcoal slurry. Plasma rifampicin levels were measured from 1 to 24 h postrifampicin ingestion. Treatment with activated charcoal significantly increased the clearance and decreased the maximum peak concentration, half-lives and area under the curves as compared with control treatment without activated charcoal.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The possible interaction of a steady-state cetirizine treatment, a nonsedating H1antihistamine, on the disposition of a single I.V. infusion of theophylline was studied in six healthy male volunteers. As a corollary, it was checked whether this single theophylline administration modified the steady-state condition of cetirizine. A three-period, two-treatment, crossover design was used, each period being separated by a washout of 1 week. Each period consisted of the oral administration of 10 mg cetirizine or of a matching placebo every 12 h for 31/2days, the last intake being followed, 1 hour later, by a single 1-h I.V. infusion of 240 mg theophylline or of placebo. The sequence of treatments (A = cetirizine + theophylline placebo, B = cetirizine placebo + theophylline, C = cetirizine + theophylline) was allotted by a double Latin-square randomization. The repeated administration of cetirizine induced a 3% decrease of the urinary elimination of unchanged theophylline; the total body clearance of theophylline was marginally (+5%) and not significantly modified. Theophylline slightly lengthened the elimination half-life of cetirizine (from 8.3 to 9.9 h), without modification of its apparent total body clearance; the half-life of cetirizine remaining in the normal range. These subtle modifications are not clinically relevant and it may, thus, be considered that cetirizine exerts no pertinent interaction on theophylline disposition.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID