Excretion of diazepam and its metabolites in human milk during withdrawal from combination high dose diazepam and oxazepam.

Abstract

The excretion of diazepam, N-desmethyldiazepam, temazepam and oxazepam in breast milk was studied during withdrawal of a 22-year-old patient from combined high dose diazepam and oxazepam therapy. Concentrations of these benzodiazepines in plasma from both the woman and her nursing infant (1 year old) were also documented. Diazepam, N-desmethyldiazepam, temazepam and oxazepam were found in the maternal plasma and milk with mean milk: plasma ratios of 0.2, 0.13, 0.14 and 0.10 respectively. It was calculated on a mg kg-1 basis that the infant received some 4.7% of the maternal dose. Diazepam could not be detected in the infant's plasma, but low levels of N-desmethyldiazepam (20 and 21 ,ug 1-1), temazepam (7 ,ug 1-1) and oxazepam (7.5 and 9.6 ,ug 1-1) were present. The infant showed no overt physical or mental symptoms of benzodiazepine intoxication.

Excretion of temazepam in breast milk [letter]

“…In milk, temazepam was detected at concentrations of 28 and 26 ,ug 1-1 in the pre and post feed samples respectively for patient number 10 only, while oxazepam was below the limit of detec- (Fuccella et al, 1977;Ochs et al, 1984). The milk:plasma ratios are in agreement with those previously reported for temazepam, as a metabolite of diazepam (Dusci et al, 1990). …”

“…To our knowledge, there is only one report of temazepam in breast milk in a woman who was taking high-dose diazepam and oxazepam (Dusci et al, 1990). Since there is widespread patient and physician concern over drug transfer into breast milk, we undertook a study to assess the excretion of temazepam into milk during the routine use of temazepam as a hypnotic in the early post partum period.…”

“…In two studies, blood samples were obtained from the nursing infants at the same time as the maternal sample. The concentrations of temazepam and oxazepam in plasma and milk were measured by high performance liquid chromatography as described previously (Dusci et al, 1990) with the minor modification that a detection wavelength of 240 nm was used. The limit of detection for both drugs was 5 p,g 1-1.…”

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).…”

“…L'anxiété, comme la dépression, est très courante à la fois pendant la grossesse et la période périnatale [20]. L'importance d'étudier le passage des benzodiazépines dans le lait maternel est liée au fait que le lait maternel constitue l'alimentation exclusive du bébé et que la plupart des études menées à ce jour [21][22][23][24][25] sur ces molécules ont révélé leur présence et celle de leurs métabolites dans le lait maternel ainsi que dans le sérum et/ou les urines du nourrisson allaité. Par ailleurs, aucune étude n'a encore fait état des conséquences à long terme sur le développement du système nerveux central du nourrisson exposé de façon chronique aux benzodiazépines par l'allaitement exclusivement.…”