Jongejan H T, Provoost A P, Wolff E D, Molenaar J C
Pediatr Res. 1986 Jan;20(1):9-14. doi: 10.1203/00006450-198601000-00003.
The effect of Cis-platin on the glomerular filtration rate and effective renal plasma flow was determined using a radioisotope clearance technique in young (3 wk old) and adult (more than 12 wk old) rats. Cis-platin was administered intravenously in dosages ranging from 2.5 to 10 mg/kg body weight, either as a single dose or fractionated over 5 consecutive days. Following either dose regimen, identical total doses of Cis-platin caused less severe nephrotoxicity in young rats than in adult ones. In adult rats fractionated dosage significantly reduced nephrotoxicity. This was not observed in young rats. The difference in nephrotoxicity between young and adult rats was due to the renal handling of Cis-platin. After a single dose of 5 and 7.5 mg/kg body weight, platinum concentrations were measured in urine and renal tissue. During the first 2 days after Cis-platin administration, up to 60% of the amount of platinum injected was excreted in the urine of both age groups. There was a marked difference, however, in renal platinum concentration between the two groups. In young rats renal platinum concentration was only 63 and 49% of that in adult rats after 5 and 7.5 mg/kg body weight, respectively. We believe that this is due to the comparatively larger renal mass in relation to body weight in the young animals. Relatively more renal tissue provides at least partial protection against nephrotoxic drugs in these young rats.
采用放射性同位素清除技术，测定顺铂对幼龄（3周龄）和成年（12周龄以上）大鼠肾小球滤过率和有效肾血浆流量的影响。顺铂以2.5至10mg/kg体重的剂量静脉给药，给药方式为单次给药或连续5天分次给药。无论采用哪种给药方案，相同总剂量的顺铂对幼龄大鼠造成的肾毒性均低于成年大鼠。在成年大鼠中，分次给药显著降低了肾毒性。而在幼龄大鼠中未观察到这种现象。幼龄和成年大鼠肾毒性的差异是由于顺铂在肾脏的处理方式不同。在单次给予5mg/kg和7.5mg/kg体重的顺铂后，分别测定尿液和肾组织中的铂浓度。在顺铂给药后的前两天，两个年龄组尿液中排出的铂量均高达注射量的60%。然而，两组之间的肾铂浓度存在显著差异。在给予5mg/kg和7.5mg/kg体重顺铂后，幼龄大鼠肾铂浓度分别仅为成年大鼠的63%和49%。我们认为，这是由于幼龄动物相对于体重而言肾脏质量相对较大。相对较多的肾组织为这些幼龄大鼠提供了至少部分针对肾毒性药物的保护。
