当前位置： SCI文献检索 > BRITISH JOURNAL OF CLINICAL PHARMACOLOGY期刊下所有文献 > Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants.

Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants.

Abstract：

AIMS:To characterize milk/plasma (M/P) ratio and infant dose, for venlafaxine (V) and its O-desmethyl metabolite (ODV), in breastfeeding women taking venlafaxine for the treatment of depression, and to determine the plasma concentration and effects of these drugs in their infants. METHODS:Six women (mean age 34.5 years, mean weight 84.3 kg) taking venlafaxine (median dose 244 mg day(-1), range 225-300 mg day(-1)) and their seven infants (mean age 7.0 months, mean weight 7.3 kg) were studied. V and ODV in plasma and milk were measured by high-performance liquid chromatography over a 12 h dose interval at steady-state. Infant exposure was estimated as the product of estimated milk production rate (0.15 l kg(-1)day(-1)) and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose. RESULTS:Mean M/PAUC values of 2.5 (range 2.0-3.2) and 2.7 (range 2.3-3.2) were calculated for V and ODV, respectively. The mean maximum concentrations (95% CI) of V and ODV in milk were 1161 (95% CI, 588, 1734) microg l(-1) and 796 (362, 1230) microg l(-1). Mean infant exposure was 3.2% (1.7, 4.7%) for V and 3.2% (1.9, 4.9%) for ODV (as V equivalents). V was detected in the plasma of one out of seven infants studied (5 microg l(-1)), while ODV was detected in four of the infants, at concentrations ranging from 3 to 38 microg l(-1). All of the infants in the study were healthy, as reported by their mothers and/or by clinical examination on the study day. CONCLUSIONS:The concentrations of V and ODV in breast milk were 2.5 and 2.7 times those in maternal plasma. The mean total drug exposure (as venlafaxine equivalents) of the breastfed infants was 6.4% (5.5-7.3%), which is below the 10% notional level of concern. There were no adverse effects in any of the infants. The data support the use of V in breastfeeding. Nevertheless, since low concentrations of ODV were detected in the plasma of four out of the seven infants studied, we recommend breastfed infants should be monitored closely. Each decision to breast feed should be made as an individual risk:benefit analysis.

journal_name

Br J Clin Pharmacol

journal_title

British journal of clinical pharmacology

authors

Ilett KF,Kristensen JH,Hackett LP,Paech M,Kohan R,Rampono J

doi

10.1046/j.0306-5251.2001.01518.x

keywords:

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

17-22

issue

eissn

0306-5251

issn

1365-2125

pii

518

journal_volume

pub_type

杂志文章

在线工具

Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants.