First-in-human pharmacokinetics of tamoxifen and its metabolites in the milk of a lactating mother: a case study.

BackgroundBreast cancer represents the most frequent neoplasm diagnosed in women of childbearing age. When the tumour is oestrogen receptor-positive, tamoxifen is among the recommended endocrine treatments. Lactating women are advised not to breastfeed while receiving tamoxifen. However, information about tamoxifen transfer into breast milk is lacking.MethodsWe measured the concentration of tamoxifen and its metabolites by liquid chromatography-tandem mass spectrometry in the milk of a nursing mother that was treated for pregnancy-associated breast cancer diagnosed a few months after delivery. She was advised not to breastfeed her child and she collected milk samples for 23 days while the baby was fed with formula.ResultsTamoxifen concentrations in milk increased reaching a maximum of 214 nM. The two active metabolitesZ-4-hydroxy-tamoxifen and Z-endoxifen, could not be quantified in milk the first days after tamoxifen intake, but increased over time and reached clinically significant levels after day 18.ConclusionThis study demonstrates for the first time in human that tamoxifen and its metabolites transfer into milk. Since tamoxifen has a complete oral bioavailability, a long half-life (>7 days) and may interfere with the normal development of the infant, mothers should not breastfeed during tamoxifen treatment.

Plasma pentraxin-3 as a marker of bioincompatibility in hemodialysis patients.

INTRODUCTION: Hemodialysis (HD)-induced inflammation has a pathogenetic role in patients with end-stage renal disease (ESRD). The aim of the present study was to assess whether pentraxin-3 (PTX3) could be a reliable biomarker of HD-induced inflammation and of membrane biocompatibility. METHODS: We prospectively enrolled 31 HD patients. Blood samples for determining PTX3, C-reactive protein (CRP), leukocytes and neutrophils were drawn from the arterial needle, before dialysis after the long dialysis-free interval (time 0), at the end of the index session (time 1) and before the next dialysis session (time 2). In 22 of 31 patients, 30 minutes after start of dialysis, PTX3 and CRP plasma levels were measured in blood collected from both the arterial and venous lines (time A - time V) of the dialyzer. In 7 of 22 patients intracellular PTX3 levels in neutrophils were measured at the end of session. RESULTS: PTX3 venous levels were significantly increased at the end of the index session compared with baseline and in blood samples drawn from the venous line compared with the arterial line of the dialyzer. At time 1, a reduction of intracellular PTX3 in neutrophils was noticed. In contrast, CRP plasma levels were stable during the HD session. CONCLUSIONS: Our findings suggest that PTX3, which is rapidly produced by several cell types and released by neutrophils upon stimulation, could be a biomarker of HD-induced inflammation and of blood-membrane bioincompatibility.