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Effect of age on the pharmacokinetics of duloxetine in women.

Abstract：

AIMS:The effect of age on duloxetine pharmacokinetics was evaluated in healthy volunteers and in patients with urinary incontinence. METHODS:Twenty-four healthy subjects (12 women 65-77 years, and 12 women 32-50 years) were given a single 40-mg oral dose of duloxetine in Study 1. Plasma concentration-time data were analysed by noncompartmental pharmacokinetic methods. Sparse plasma samples were obtained from patients with urinary incontinence treated in two phase II studies: 70 women (24-77 years) who received duloxetine 20 mg day(-1), 30 mg day(-1), or 40 mg day(-1) in Study 2A and 128 women (28-64 years) who received duloxetine 20 mg day(-1), 40 mg day(-1), or 80 mg day(-1) in Study 2B. Based upon the combined data, a model was developed to characterize population pharmacokinetics of duloxetine using the nonlinear mixed-effects modelling program (NONMEM). RESULTS:In Study 1, the elderly (> or = 65 years) exhibited a statistically significant slower elimination rate constant lambdaz compared with younger subjects [elderly-younger difference = -0.022 h(-1)[95% confidence interval (CI) -0.036, -0.008]]. However, no statistically significant differences in either CL/F [elderly-younger difference = -17.4 l h(-1) (95% CI -41.1, 6.23)] or V/F [elderly-younger difference = 115.9 l (95% CI -168.6, 400.4)] were observed. The population pharmacokinetic analysis of Studies 2A and 2B revealed that the CL/F of duloxetine decreased with increasing age. Despite statistical significance, the age effect only accounted for 3% of the interindividual variability in CL/F and unexplained sources of the variation in clearance were still substantial (> 50%). Adverse events were generally mild to moderate, and the incidence of adverse events was generally similar in elderly and non-elderly participants in these studies. CONCLUSIONS:Whereas the results suggest that age has an effect on duloxetine pharmacokinetics, primarily reflected as a slower lambdaz in the elderly, the magnitude of mean changes in CL/F, or V/F was small relative to the large interindividual variation in pharmacokinetics. Elderly participants had a safety profile of duloxetine comparable to their younger counterparts. Specific dose recommendations for duloxetine in the elderly are not warranted.

journal_name

Br J Clin Pharmacol

journal_title

British journal of clinical pharmacology

authors

Skinner MH,Kuan HY,Skerjanec A,Seger ME,Heathman M,O'Brien L,Reddy S,Knadler MP

doi

10.1046/j.1365-2125.2003.01963.x

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

54-61

issue

eissn

0306-5251

issn

1365-2125

pii

1963

journal_volume

pub_type

临床试验,杂志文章,多中心研究,随机对照试验

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Effect of age on the pharmacokinetics of duloxetine in women.