Strolin Benedetti M, Moro E, Frigerio E, Jannuzzo M G, Roncucci R, Caldwell J
Research and Development, Farmitalia Carlo Erba-Erbamont Group, Milan, Italy.
Biochem Pharmacol. 1990 Oct 15;40(8):1719-23. doi: 10.1016/0006-2952(90)90347-n.
The plasma pharmacokinetics and urinary elimination of the enantiomers of indobufen, a novel platelet aggregation inhibitor, have been studied in rats and mice given either the racemic compound or the individual enantiomers (rat 8 mg/kg racemate, 4 mg/kg enantiomers; mouse 25 mg/kg racemate, 12.5 mg/kg enantiomers). Enantiospecific analysis of indobufen in plasma and urine was achieved by HPLC of its L-leucinamide diastereoisomers. In rat, the two enantiomers have very different plasma elimination half lives (S, 3.9 hr; R, 12.2 hr), irrespective of the optical form administered. The plasma concentration-time curves of S-indobufen were identical after racemic or S-indobufen, but the plasma levels of R-indobufen were lower after the R-enantiomer than after the racemate. Urinary recovery of free and conjugated indobufen was less than 3% of the dose, independent of the optical form administered. In the mouse, R-indobufen was cleared from plasma more rapidly than its S-antipode (elimination T1/2 R, 2.5 hr; S, 3.8 hr) but differences were smaller than those seen in the rat. The plasma concentration-time curves of the S-enantiomer were the same after racemic or S-indobufen, but levels of its R-antipode were much lower when it was given alone than after administration of the racemate. The urinary recovery of free and conjugated indobufen also exhibited enantioselectivity, with preferential elimination of the S-enantiomer.
在给予消旋化合物或单一对映体（大鼠8mg/kg消旋体、4mg/kg对映体；小鼠25mg/kg消旋体、12.5mg/kg对映体）的大鼠和小鼠中，研究了新型血小板聚集抑制剂吲哚布芬对映体的血浆药代动力学和尿排泄情况。通过其L-亮氨酰胺非对映异构体的高效液相色谱法实现了血浆和尿液中吲哚布芬的对映体特异性分析。在大鼠中，无论给予何种光学形式，两种对映体的血浆消除半衰期差异很大（S型，3.9小时；R型，12.2小时）。消旋吲哚布芬或S-吲哚布芬给药后，S-吲哚布芬的血浆浓度-时间曲线相同，但R-吲哚布芬对映体给药后其血浆水平低于消旋体给药后。游离和结合型吲哚布芬的尿回收率均低于给药剂量的3%，与给药的光学形式无关。在小鼠中，R-吲哚布芬从血浆中的清除速度比其S-对映体快（消除半衰期R型，2.5小时；S型，3.8小时），但差异小于大鼠。消旋吲哚布芬或S-吲哚布芬给药后S-对映体的血浆浓度-时间曲线相同，但其R-对映体单独给药时的水平远低于消旋体给药后。游离和结合型吲哚布芬的尿回收率也表现出对映体选择性，S-对映体优先被消除。
