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  • Title: The comparative disposition of nomifensine (Merital) in the pregnant and non-pregnant rat.
    Author: Ings RM.
    Journal: Arch Int Pharmacodyn Ther; 1979 Dec; 242(2):180-95. PubMed ID: 543752.
    Abstract:
    The disposition of radioactivity from 14C-nomifensine has been compared in pregnant and non-pregnant female rats by examining plasma profiles, the qualitative tissue distribution (whole body autoradiography) and the quantitative tissue distribution of radioactivity. The clearance of radioactivity of 14C-nomifensine from the plasma of pregnant and non-pregnant rats was similar and was complex with secondary peaks and plateaux after both oral and intravenous dosing. Maximum plasma levels (mean +/- S.D., 0.20 +/- 0.05 and 0.22 +/- 0.02 microgram equivalents nomifensine/ml plasma for pregnant and non-pregnant rats respectively) occurred at 30 to 45 min after oral dosing. The biological half-life of radioactivity in plasma was between 4 and 5 hr for both routes of administration, although there was an additional rapid initial phase (t 1/2 approx. 20 min) after intravenous dosing. Whole body autoradiography also showed a very similar tissue distribution pattern of radioactivity between pregnant and non-pregnant rats with extensive distribution from blood into tissue. Only traces of radioactivity from 14C-nomifensine were seen to cross the placenta into the foetuses of 15-day pregnant rats and these rapidly cleared with time. Slightly higher amounts were seen to cross the foetuses of 18-day pregnant rats and radioactivity was seen in the foetal brain, heart, liver and lung. Quantitative tissue distribution studies confirmed these qualitative findings. The biological half-life of radioactivity in both adult and foetal tissues was approximately 5 hr, except for adult livers where a longer half-life of radioactivity of approximately 10 hr was found.
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