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Objective: To report a case of the transfer of probenecid and cephalexin into human milk. Case Summary: A breast-fed infant of a 30-year-old woman being treated with oral probenecid and cephalexin for a breast infection developed severe diarrhea and associated symptoms. To investigate whether the maternal drug treatment was causative, milk was collected over a dose interval at steady-state, and concentrations of probenecid and cephalexin were measured by HPLC. The average concentrations of probenecid and cephalexin in milk were 964 and 745 μg/L, respectively, corresponding to absolute and relative infant doses of 145 μg/kg/day and 0.7% for probenecid and 112 μg/kg/day and 0.5% for cephalexin. The infant's adverse effects were rated as possible for probenecid and probable for cephalexin based on the Naranjo probability scale. Discussion: On the basis of the calculated relative infant doses for both probenecid and cephalexin in milk and the notional 10% level of concern for infant exposure, neither drug would be expected to cause significant systemic effects. However, local adverse effects, notably diarrhea, were observed. The Naranjo probability scale rating suggested that cephalexin was more likely than probenecid to be the cause of the infant's diarrhea. Conclusions: When using cephalexin/probenecid to treat breast infections in lactating women, clinicians should anticipate the possibility of adverse gastrointestinal effects in the breast-fed infant.

The progesterone receptor (PR) is an important regulator of female reproduction. Consequently, PR modulators have found numerous pharmaceutical utilities in women's reproductive health. In the process of identifying more receptor-specific and tissue-selective PR modulators, we discovered a novel nonsteroidal, 6-aryl benzoxazinone compound, PRA-910, that displays unique in vitro and in vivo activities. In a PR/PRE reporter assay in COS-7 cells, PRA-910 shows potent PR antagonist activity with an IC50 value of approximately 20 nM. In the alkaline phosphatase assay in the human breast cancer cell line T47D, PRA-910 is a partial progesterone antagonist at low concentrations and is also an effective PR agonist at higher concentrations (EC50 value of approximately 700 nM). PRA-910 binds to the human PR with high affinity (K d=4 nM) and was previously shown to exhibit greater than 100-fold selectivity for the PR versus other steroid receptors. In the adult ovariectomized rat, PRA-910 is a potent PR antagonist. It inhibits progesterone-induced uterine decidual response with an ED50 value of 0.4 mg/kg, p.o., and reverses progesterone suppression of estradiol-induced complement C3 expression with potency similar to RU-486. In the nonhuman primate, however, PRA-910 is a PR agonist. The effect on endometrial histology strongly resembles that of progesterone. This unique compound also suppresses estradiol-induced epithelial cell proliferation and both estrogen and progesterone receptor expression in the uterine endometrium as a PR agonist would. In summary, PRA-910 is a structurally and biologically novel selective PR modulator with either PR agonist or antagonist activity, depending on context, concentration, and species.

OBJECTIVE: According to DSM-IV criteria, dissociative symptoms in borderline personality disorder (BPD) occur in response to stress. Empirical evidence is, however, lacking. METHOD: Using ambulatory monitoring, we assessed dissociative symptoms and subjective ratings of stress every 60 min for 48 h on a palmtop computer in BPD-patients (n = 51), clinical controls (CC; major depression n = 25; panic disorder n = 26), and healthy controls (HC; n = 40). Data analyses were primarily based on hierarchical linear models. RESULTS: In all groups, states of increased stress were paralleled by increased scores of dissociation, thus confirming the hypothesized association between stress and dissociation. The increase in dissociation was more pronounced in BPD-patients when compared with CC and HC. Additionally, BPD-patients reported heightened dissociative experience compared with CC and HC, even after controlling for stress. CONCLUSION: Our data suggest that BPD-patients might be prone to dissociation when experiencing stress and are characterized by a generally heightened level of dissociation.