Roberts G W, Nation R L, Jarvinen A O, Martin A J
Department of Pharmacy, Adelaide Children's Hospital, North Adelaide, 5006, Australia.
Br J Clin Pharmacol. 1993 Oct;36(4):372-5. doi: 10.1111/j.1365-2125.1993.tb00380.x.
A non-blinded, randomized, cross-over investigation of the pharmacokinetic interaction between tobramycin and ticarcillin was performed in 18 healthy cystic fibrosis (CF) patients with normal renal function. On consecutive mornings the patients were given either tobramycin intravenously (i.v.) over 3-5 min (TOB phase), or tobramycin i.v. over 3-5 min followed immediately by ticarcillin infused i.v. over 20-30 min (TOB+TIC phase). Capillary blood samples were taken 30 min and 330 min after administration of the tobramycin dose in each phase. Tobramycin was measured in serum by fluorescence polarization immunoassay (TDx). There were decreases in serum tobramycin concentrations of 11% at 30 min (P < 0.001) and 330 min (P = 0.012) when measured in the presence of ticarcillin. No difference in elimination half-life was found (TOB phase 95 +/- 13 min, TOB+TIC phase 95 +/- 13 min, P = 0.86). The volume of distribution and clearance of tobramycin increased by 14% (P < 0.001) and 13% (P < 0.001), respectively, in the presence of ticarcillin. This interaction appears to be of minor clinical importance but pharmacokinetic studies of tobramycin should exclude concurrent use of ticarcillin.
在18名肾功能正常的健康囊性纤维化(CF)患者中进行了一项关于妥布霉素和替卡西林药代动力学相互作用的非盲、随机、交叉研究。在连续的早晨,患者分别接受静脉注射(i.v.)妥布霉素3 - 5分钟(TOB阶段),或静脉注射妥布霉素3 - 5分钟后紧接着静脉输注替卡西林20 - 30分钟(TOB + TIC阶段)。在每个阶段给予妥布霉素剂量后30分钟和330分钟采集毛细血管血样。通过荧光偏振免疫测定法(TDx)测定血清中的妥布霉素。在有替卡西林存在的情况下测量时,血清妥布霉素浓度在30分钟时降低了11%(P < 0.001),在330分钟时降低了11%(P = 0.012)。未发现消除半衰期有差异(TOB阶段95 ± 13分钟,TOB + TIC阶段95 ± 13分钟,P = 0.86)。在有替卡西林存在的情况下,妥布霉素的分布容积和清除率分别增加了14%(P < 0.001)和13%(P < 0.001)。这种相互作用似乎在临床上重要性较小,但妥布霉素的药代动力学研究应排除与替卡西林同时使用的情况。