Weir M R, Keniston R C, Enriquez J I, McNamee G A
Department of Pediatrics, Madigan Army Medical Center, Tacoma, WA 98431-5406.
Vet Hum Toxicol. 1990 Jun;32(3):235-8.
The renal toxicity of gentamicin is altered by dietary protein modifications, bicarbonate and acetazolamide administration, magnesium supplementation, polyaspartic acid, piperacillin, hypercalcemia and calcium channel blockers. Renal tissue gentamicin levels have an undetermined role. Reduction of renal pyridoxal 5'-phosphate (PLP- by gentamicin has been shown, as has protection from nephrotoxicity by administration of vitamin B6. To explore an interaction between gentamicin and vitamin B6, gentamicin (5 mg/kg) was given to rabbits by ip injection, with either pyridoxine (10 mg) or isovolemic saline for 3 weeks. There was not a difference between gentamicin levels for animals given gentamicin and pyridoxine versus those given gentamicin and saline. Gentamicin administration led to a 47% fall (p = .0001) in plasma PLP levels. Three days after the last gentamicin administration, the animals maintained a 32% decrease from the pre-gentamicin baseline values (p = 0.02). When pyridoxine was administered concurrently with gentamicin, the PLP rise of 49% was significant (p = 0.001). The mean level after the study (6%) was not significantly lower than baseline (p = .6). We believe that gentamicin interfers with vitamin B6 metabolism, but that vitamin B6 status does not affect levels of gentamicin. A number of drugs affect B6 levels, creating the potential for hypovitaminosis B6 to be an important mechanism of drug-drug interaction in seriously ill patients, particularly in sick newborns or the elderly with lower average PLP levels.
庆大霉素的肾毒性会因饮食蛋白质的改变、碳酸氢盐和乙酰唑胺的给药、镁补充剂、聚天冬氨酸、哌拉西林、高钙血症和钙通道阻滞剂而发生变化。肾组织中的庆大霉素水平作用尚不明确。已证实庆大霉素会降低肾组织中的磷酸吡哆醛(PLP)水平,同时也表明补充维生素B6可预防肾毒性。为探究庆大霉素与维生素B6之间的相互作用,给家兔腹腔注射庆大霉素(5mg/kg),同时分别给予吡哆醇(10mg)或等容量生理盐水,持续3周。给予庆大霉素和吡哆醇的动物与给予庆大霉素和生理盐水的动物相比,庆大霉素水平并无差异。给予庆大霉素导致血浆PLP水平下降47%(p = 0.0001)。在最后一次给予庆大霉素3天后,动物的PLP水平较庆大霉素给药前的基线值仍降低32%(p = 0.02)。当吡哆醇与庆大霉素同时给药时,PLP水平显著升高49%(p = 0.001)。研究结束时的平均水平(6%)与基线相比无显著降低(p = 0.6)。我们认为庆大霉素会干扰维生素B6的代谢,但维生素B6状态并不影响庆大霉素的水平。许多药物会影响B6水平,这使得维生素B6缺乏成为重症患者,尤其是患病新生儿或平均PLP水平较低的老年人中药物相互作用的一个重要机制。