Abstract
These studies comprehensively evaluate the distribution of [14C]olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno(2,3-b)-1,5)benzodiazepin e, CAS 132539-06-1, LY170053) a novel anti-schizophrenic compound, following single oral dose administration in male Fischer 344 rats, and pregnant and non-pregnant lactating female CD rats. The disposition of radiocarbon was determined and tissue pharmacokinetics evaluated in male Fischer 344 rats following a single oral 8 mg/kg dose at 2, 6, 24, 48, 72, and 96 h postdose using quantitative whole-body autoradiographic (QWBA) techniques in conjunction with image analysis. This study demonstrated that [14C]olanzapine and/or metabolites were rapidly absorbed and widely distributed with a tmax of 2 h postdose in most tissues. Persistent but declining concentrations of radiocarbon were detected in feces, kidney, liver, and Harderian, preputial, and thyroid glands at 96 h postdose. Placental transfer of [14C]olanzapine was evaluated at 0.5, 1, 3, 6, and 24 h postdose on gestation day 12, the mid-point of organogenesis, by tissue dissection and liquid scintillation spectroscopy (LSC) and on gestation day 18, a time which enabled visualization of fetal tissues by whole-body autoradiography...Continue Reading