Pharmacokinetics of fluoxetine and norfluoxetine in pregnancy and lactation

被引:156
作者
Heikkinen, T
Ekblad, U
Palo, P
Laine, K
机构
[1] Univ Turku, Dept Pharmacol & Clin Pharmacol, FIN-20520 Turku, Finland
[2] Univ Turku, Dept Obstet & Gynaecol, FIN-20520 Turku, Finland
[3] Univ Turku, Cent Hosp, FIN-20520 Turku, Finland
关键词
D O I
10.1016/S0009-9236(02)17634-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: The aim of this prospective clinical trial was to investigate the pharmacokinetics of fluoxetine and its active metabolite, norfluoxetine, during pregnancy, delivery, and lactation in mothers and their infants. Methods: Eleven mothers taking fluoxetine and their infants were enrolled in the study. A control group of 10 women who were not taking psychotropic medication were prospectively matched for confounding obstetric characteristics at the time of delivery. Trough plasma samples and breast milk samples were collected from mother-infant pairs during pregnancy, at delivery, and up to 2 months after delivery in the fluoxetine group. The pregnancy outcome was recorded, and the growth and neurologic development of the children were followed up to the age of 1 year in both study groups. Results: The fluoxetine dose from 20 mg to 40 mg once daily resulted in relatively low trough fluoxetine-norfluoxetine concentrations during pregnancy (range, 317-850 nmol/L). The mean norfluoxetine/fluoxetine metabolic ratio was 2.4-fold higher during late pregnancy than at 2 months after delivery (P = .0072). At delivery, the infant plasma fluoxetine and norfluoxetine concentrations were 65% and 72%, respectively, of those found in mothers. The mean estimated infant exposures from breast milk to fluoxetine-norfluoxetine were 2.4% and 3.8% of the maternal weight-adjusted daily dose at age 2 weeks and age 2 months, respectively. The pregnancy outcome, as well as the growth and neurologic development of all infants up to I year of age, was normal. Conclusion: Common clinical doses of fluoxetine resulted in relatively low concentrations of fluoxetine during pregnancy, which can be explained at least partly by increased demethylation of fluoxetine by cytochrome P450 (CYP) 2D6. This might indicate that these low blood levels could lead to therapeutic failure, and clinicians should be alert to this possibility so that depression in pregnancy is not undertreated.
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页码:330 / 337
页数:8
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