Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk.

Abstract

1 Alprazolam, a triazolobenzodiazepine, is extensively prescribed for the treatment of anxiety disorders, which predominantly affect women of child-bearing age. The purpose of the present study was to assess the pharmacokinetics of alprazolam and its two hydroxylated metabolites: 4-hydroxy-alprazolam and a-hydroxy-alprazolam in lactating human volunteers and to test the predictability of four recently reported models for drug transfer into milk based on physicochemical properties. 2 Multiple milk and serum samples in eight lactating subjects were collected up to 36 h following single oral doses of 0.5 mg alprazolam; suckling of the infant was discontinued after drug administration. 4-Hydroxy-alprazolam was the predominant metabolite in serum samples while a-hydroxy-alprazolam was not detected.

Passage des benzodiazépines dans le lait maternel : aspects cliniques et analytiques

“…Cette éva-luation devant reposer sur des informations scientifiques validées et actualisées, il est donc indispensable de savoir doser les médicaments dans le lait, en particulier ceux pouvant poser problème chez le nouveau-né ou le nourrisson allaité, comme c'est le cas des benzodiazépines et des psychotropes en général. Concernant les techniques HPLC publiées [24,63], le principe évoqué par les auteurs a été similaire au nôtre : valider une méthode analytique déjà utilisée en routine pour les échan-tillons plasmatiques. Une des deux techniques publiées [24] présente une LOQ semblable à la nôtre (diazépam 50 ng/mL).…”

“…Une des deux techniques publiées [24] présente une LOQ semblable à la nôtre (diazépam 50 ng/mL). Pour la seconde technique [63], elle concerne l'alprazolam, molécule à demi-vie courte et donc théoriquement sans inté-rêt pour le suivi thérapeutique des nourrissons.…”

Utility of noninvasive biomatrices in pharmacokinetic studies

“…It was observed that the milk levels of alprazolam were in close agreement with that of serum with the mean milk to serum ratio (M/S ratio) of 0.36 ± 0.11. The mean residence time of alprazolam in milk was 18.93 ± 7.03 h, which is very close to that of serum, 16.42 ± 4.69 h (Oo et al ., ).…”

“…Oo et al . () developed and validated a HPLC‐UV method for the determination of alprazolam in human milk. To 2 mL of milk 5 mL of acetonitrile was added to precipitate proteins.…”

“…Owing to the advances in extraction methods, SPE is most preferred as the samples obtained are much cleaner compared with other extraction methods. Oo et al (1995) developed and validated a HPLC-UV method for the determination of alprazolam in human milk. To 2 mL of milk 5 mL of acetonitrile was added to precipitate proteins.…”