Disposition of the novel anti-schizophrenic drug [14C]olanzapine in male Fischer 344 and female CD rats following single oral dose administration

Arzneimittelforschung. 1998 May;48(5):446-54.


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 (WBA). The placental transfer studies indicated that all tissues analyzed had a tmax of 1 or 3 h postdose with maternal liver consistently containing high concentrations of radiocarbon. Embryos contained measurable concentrations of radiocarbon throughout the time course of these studies confirming that [14C]olanzapine and/or its metabolites crossed the placenta. Additionally, the disposition of [14C]olanzapine in milk and plasma of lactating female CD rats confirmed pup exposure through milk ingestion.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacokinetics*
  • Area Under Curve
  • Autoradiography
  • Benzodiazepines
  • Female
  • Image Processing, Computer-Assisted
  • Male
  • Maternal-Fetal Exchange
  • Milk / metabolism
  • Olanzapine
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / pharmacokinetics
  • Pregnancy
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Strains
  • Tissue Distribution


  • Antipsychotic Agents
  • Benzodiazepines
  • Pirenzepine
  • Olanzapine