摘要:

Twenty‐four men and 24 women ages 20–77 years received a single 15 mg oral dose of buspirone followed by 4 days of 15 mg tid administration. Plasma concentrations of buspirone and 1‐pyrimidinylpiperazine following both single and multiple dosing were determined by RIA and GCMS, respectively. There were no significant differences between the young and elderly of either gender with regard to buspirone AUC, Cmax, Tmax and half‐life values. The 1‐PP AUC values were higher for young of either gender compared to the corresponding group of ederly subjects and the 1‐PP Cmax values were higher for women than men. These differences are unlikely to be of clinical significance. The buspirone and 1‐PP AUC values for a dosing interval during multiple dosing are not significantly different than the respective single dose AUC values. Buspirone treatment was well‐tolerated by all subjects even though the 45 mg/day dose was 3 times the recommended starting dose in clinical practice. Overall, the lack of marked or consistent differences in buspirone or 1‐PP pharmacokinetics in elderly subjects compared to younger subjects of the same gender suggest there is no need to alter the initial dose of buspirone based sole

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03240.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The effect of food on the relative bioavailability of an erythromycin particles‐in‐tablet formulation was studied in 27 healthy volunteers, using a four‐way, crossover study design with the following treatments: one or two erythromycin capsules USP (Eryc®, Parke‐Davis), or one polymer‐coated erythromycin particles‐in‐tablet (PCE®, Abbott) administered fasting or with a high‐fat meal. Under fasting conditions the erythromycin particles‐in‐tablet and erythromycin capsule formulations are bioequivalent based on similar tmaxand dose‐normalized Cmaxand AUC values. The rate and extent of absorption from the particles‐in‐tablet formulation, however, are dramatically reduced following administration with a meal. Mean Cmaxand AUC values decreased by 73% and 72%, respectively, and seven subjects had no detectable erythromycin plasma concentrations for 16 hours following administration of the particles‐in‐tablet formulation with the high‐fat meal. Greater than 40% of the subjects had nonfasting Cmaxand AUC values that were less than 10% of those values following administration of the dose fasting. Cmaxand AUC values in nonfasting subjects were within 75% to 125% of fasting values in only two and one of 27 subjects, respectively. The erythromycin particles‐in‐tablet formulation therefore

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03241.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Because hydroxyzine hydrochloride is frequently used to tranquilize patients, who are receiving narcotic analgesics for pain relief, its effect alone and in combination with meperidine on arterial blood gases and ventilation in patients at rest was evaluated in 65 healthy volunteers, who gave informed consent. Hydroxyzine hydrochloride, 1.5 mg/kg IV given over 30 seconds, caused no decrease but rather a significant (P<.001) increase in Pao2and no increase in Paco2and/or pH at 5, 10, 20, 30, and 60 minutes (N = 29; mean age = 47.0 years). Meperidine, 1.5 mg/kg IV given over 30 seconds, caused a significant (P<.01) reduction in Pao2at 5 minutes indicating ventilatory depression but no increase in Paco2and/or pH (N = 19; mean age = 32.4 years). The combination of the same doses of hydroxyzine with meperidine IV caused a significantly greater decrease in Pao2only at 10 minutes but a greater increase in Paco2and pH at all times for 60 minutes than did meperidine alone (N = 17; mean age = 39.5 years), which indicates greater ventilatory depression with the combination than with hydroxyzine alone. However, Pao2, Paco2and pH remained within the awake normal ranges for Pao2, Paco2, and pH for the age group of volunteers even at 10 minutes after IV injection of the drug combination when most of the volunteers were asleep. In conclusion, hydroxyzine even when given IV in excess of the maximum IM therapeutic doses caused no changes in Pao2, Paco2or pH, which would indicate clinically important ventilatory depression. Furthermore, blood gases remained in the normal awake range even after the combined IV administration of hydroxyzine and meperidine in excess of the maximum IM therapeutic doses.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03242.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The influence of 17 days of administration of fluvoxamine or clovoxamine, two new antidepressant agents, on the kinetics of a single intravenous dose of digoxin, and on self‐rated parameters of sedation, mood, and sleep, was evaluated in a series of healthy volunteers. In the fluvoxamine study, subjects received fluvoxamine, 100 mg daily, or matching placebo for 17 consecutive days in a crossover design. For the clovoxamine study, subjects received clovoxamine, 150 mg daily, or placebo for 17 days. All treatments were double blind. At the end of each treatment, digoxin kinetics were evaluated following a single 1.25 mg intravenous dose. Compared to the placebo condition, fluvoxamine had no significant influence on digoxin elimination half‐life (57 vs 47 hours), volume of distribution (10.5 vs 10.3 liters/kg), total clearance (2.4 vs 3.0 ml/min/kg), or 72 hour urinary excretion (33 vs 37 percent of the dose). Likewise clovoxamine did not alter digoxin elimination half‐life (39 vs 40 hours), volume of distribution (10.7 vs 10.2 liters/kg), or total clearance 3.4 vs 3.4 ml/min/kg). 72 hour urinary excretion of digoxin was slightly increased by clovoxamine (41 vs 50 percent of the dose, P<.05). Self‐ratings indicated a sedating effect of fluvoxamine, with reports of difficulty attaining morning alertness. These effects were not reported with clovoxamine. Thus clovoxamine and fluvoxamine appear to have differential effects on sleep and alertness in healthy volunteers. However, neither have an important influence on the kinetics of

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03243.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Book reviewed in this article:Biotechnologically Derived Medical Agents: The Scientific Basis of Their RegulationEdited by John L. GueriguianHypercholesterolemia: Clinical and Therapeutic Implications (Atherosclerosis Reviews, Vol. 18)Edited by Joseph Stokes III, and Mario Mancini

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03244.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY