Perez de la Cruz M J, Cadórniga R, Ochoa M C, Albarran I, Herrero-Vanrell R, Pastoriza P
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain.
Biopharm Drug Dispos. 1998 Sep;19(6):407-12. doi: 10.1002/(sici)1099-081x(199809)19:6<407::aid-bdd120>3.0.co;2-t.
The study used 36 New Zealand white rabbits organized into three groups of 12 animals each. Group I received gentamicin; Group II received joint administration of gentamicin and calcium chloride and Group III received gentamicin, calcium chloride and verapamil. All the drugs were administered over 16 day periods. Groups I and II were divided in two subgroups, one subgroup receiving the treatment in winter and the other in summer. The results obtained for Group I indicate that there is an influence of the seasonal period on the gentamicin elimination and/or distribution. Mean plasma levels of the antibiotic at steady-state as well as the amounts of gentamicin accumulated in renal tissue are higher in winter than in summer. On the other hand, when calcium was administrated with the antibiotic, no significant circannual variations were observed in the renal toxicity of gentamicin. Under our study conditions the presence of calcium diminishes gentamicin plasma levels and the amount accumulated in kidney. Calcium, probably, generated a diminution in renal damage and consequently gentamicin renal excretion increases. The differences between Group II and Group III are due to the effect of verapamil. This agent blocks the calcium channels reducing the calcium protective effect on the nephrotoxicity of gentamicin.
该研究使用了36只新西兰白兔，分为三组，每组12只。第一组接受庆大霉素治疗；第二组接受庆大霉素和氯化钙联合给药，第三组接受庆大霉素、氯化钙和维拉帕米。所有药物均给药16天。第一组和第二组再分为两个亚组，一个亚组在冬季接受治疗，另一个亚组在夏季接受治疗。第一组获得的结果表明，季节对庆大霉素的消除和/或分布有影响。冬季稳态时抗生素的平均血浆水平以及肾组织中积累的庆大霉素量均高于夏季。另一方面，当钙与抗生素一起给药时，未观察到庆大霉素肾毒性有明显的年周期变化。在我们的研究条件下，钙的存在会降低庆大霉素的血浆水平和肾脏中积累的量。钙可能减少了肾脏损伤，因此庆大霉素的肾排泄增加。第二组和第三组之间的差异是由于维拉帕米的作用。该药物阻断钙通道，降低了钙对庆大霉素肾毒性的保护作用。
