Pharmacokinetic studies of trimoprostil in rats. (II). Blood level profile and tissue distribution during and after the consecutive oral administration of trimoprostil.
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<SUP>3</SUP>H-trimoprostil labeled at a C-11 methyl position was repeatedly given to rats of two sexes at a daily oral dose of 100 μg/kg for 14 days. The blood level profile and tissue accumulation of radioactivity were examined during and after the multiple administration.<BR> 1. Blood level profile<BR> The time course of <SUP>3</SUP>H in the blood showed two peaks, one approximately 30 ?? 45 min and another 4 hr after respective dosing, then the blood concentration gradually decreased.<BR> The peak and minimum concentrations (24 hr level after each dosing) during the multiple administration were in the range of 1 ?? 2.1 times and 2.4 ?? 3.6 times higher than those observed after a single administration respectively.<BR> 2. Tissue accumulation<BR> The accumulation ratio (a ratio of concentration of <SUP>3</SUP>H at 24 hr after the last dose of multiple administration, over 24 hr concentration after a single dosing) in each tissue was the same or lower in comparison to that (3.6 ?? 10) of the blood.<BR> Within 21 days after the cessation of multiple administration, <SUP>3</SUP>H concentration in almost all the tissues other than the white fat pad decreased below the respective detection limits or 24 hr-levels after a single administration (100 μg/kg). The concentration of <SUP>3</SUP>H in the fat pad on Day 21 after the last dose was as low as 20 ?? 24%of the level on day 1.
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