Understanding the preclinical toxicity profile of standard of care oncology agent carboplatin: Effect of a 7-cycle treatment on bone marrow and peripheral cell depletion and recovery in the Han Wistar rat

s / Toxicology Letters 229S (2014) S40–S252 S241 formed to evaluatewhether sex-dependent differences exist in this context. Nevirapine-containing solutions were perfused through the intestine, in a specially designed chamber, or incubated with liver slices frommale and female wistar rats. The levels of NVP and its Phase I metabolites were quantified by HPLC-UV. Liver incubationexperimentsyielded themetabolites2-, 3-, 8-, and12-OH-NVP. 12-OH-NVP and 2-OH-NVP were the major metabolites in males and females, respectively. Inter-sex differences in the metabolic profile were also detected in the intestine. Whilst 3and 12-OHNVP were only found in male rats, 2-OH-NVP levels were higher in females, both inextraluminal (p<0.01) and intraluminalmedia. The metabolite 8-OH-NVP was not detected in the intraluminal media, nor in the extraluminal media, from either males or females. An extra-hepatic contribution toNVP biotransformationwas observed herein. In particular, NVP biotransformation in the intestine generated a metabolite profile different from the liver. Moreover, important inter-sex differences were detected in both organs, providing further clues to the sex-dimorphic profile of NVP toxicity. http://dx.doi.org/10.1016/j.toxlet.2014.06.803