Bunke C M, Aronoff G R, Brier M E, Sloan R S, Luft F C
Clin Pharmacol Ther. 1983 Jul;34(1):110-6. doi: 10.1038/clpt.1983.138.
To establish therapeutic guidelines for tobramycin use in patients receiving continuous ambulatory peritoneal dialysis (CAPD), we studied tobramycin single-dose kinetics in CAPD patients. Tobramycin was studied after a 1.5-mg/kg dose given either intravenously (TOB-IV) or intraperitoneally (TOB-IP). TOB-IV provided a plasma concentration above 3 mg/l at 12 hr with a t 1/2 of 39.5 hr. When tobramycin was given intraperitoneally, 52% of the dose was absorbed; peak plasma concentrations were only 1.8 mg/l, and the t 1/2 was 35 hr. CAPD accounted for only 15% to 20% of total body clearance in both groups. The kinetic principle of superposition was used to predict plasma concentrations after repeated TOB-IP. A model using once-a-day dosing predicted that a loading dose of 4 mg/kg followed by 1.5 mg/kg would achieve steady-state plasma concentrations of 2.8 to 4.2 mg/l. Another model using tobramycin in each exchange predicted that a loading dose of 3 mg/kg followed by 0.3 mg/kg would provide steady-state plasma concentrations of 2.8 to 3.1 mg/l. These data should be useful in treating CAPD patients with tobramycin who have nonperitoneal gram-negative aerobic bacterial infections, as well as those who require the drug for peritonitis.
为制定持续性非卧床腹膜透析(CAPD)患者使用妥布霉素的治疗指南,我们研究了CAPD患者的妥布霉素单剂量动力学。在给予1.5mg/kg剂量的妥布霉素后,分别通过静脉注射(TOB-IV)或腹腔内注射(TOB-IP)进行研究。TOB-IV给药后12小时血浆浓度高于3mg/l,半衰期为39.5小时。当妥布霉素通过腹腔内注射给药时,52%的剂量被吸收;血浆峰值浓度仅为1.8mg/l,半衰期为35小时。两组中CAPD清除率仅占全身清除率的15%至20%。采用叠加动力学原理预测重复TOB-IP给药后的血浆浓度。每日一次给药的模型预测,4mg/kg的负荷剂量后接1.5mg/kg将使血浆稳态浓度达到2.8至4.2mg/l。另一个在每次交换中使用妥布霉素的模型预测, 3mg/kg的负荷剂量后接0.3mg/kg将使血浆稳态浓度达到2.8至3.1mg/l。这些数据对于治疗患有非腹膜革兰氏阴性需氧菌感染的CAPD患者以及需要该药物治疗腹膜炎的患者应该是有用的。