Guggenbichler J P, Pillwein K, Schabel F, Rohrer R
Padiatr Padol. 1981;16(4):393-402.
Inadequate therapeutic results in the treatment of bacterial infections in patients with Cystic Fibrosis prompted a reevaluation of pharmacokinetic parameters of orally and parenterally administered drugs in these patients. Gentamicin, Azlocillin and Ticarcillin are eliminated faster in patients with Cystic Fibrosis. Serum concentrations show a rapid decrease over 60 to 90 minutes and surpass MIC values of Pseudomonas isolates for a maximum of only 60 minutes. 70% to 90% of the administered amount of drug is eliminated within two hours in the urine. Concomitantly determined clearance rates for creatinine didn't show abnormalities, however they pointed towards an additional tubular secretion of Gentamicin which is not seen in healthy controls. Cephalexin, Epicillin and both components of Cotrimoxazol show a delay in oral absorption. The renal elimination of Cephalexin and Trimethoprim is unaltered, but the excretion of Epicillin and Sulfametrol is enhanced again. This is seen by a delay and decrease in the maximal serum concentration (Cmax), but increased urine recovery. Doubling of the dose of gentamicin administered as i. v. infusion over 45 to 60 minutes results in smooth serum curve, the MIC values of most encountered organisms are surpassed for 3 hours and more. The clinical applicability of this recommendation however awaits further investigations concerning efficacy and safety.
囊性纤维化患者细菌感染的治疗效果不佳,促使人们重新评估这些患者口服和注射用药物的药代动力学参数。囊性纤维化患者体内庆大霉素、阿洛西林和替卡西林的清除速度更快。血清浓度在60至90分钟内迅速下降,超过铜绿假单胞菌分离株的最低抑菌浓度(MIC)值的时间最长仅为60分钟。给药量的70%至90%在两小时内从尿液中清除。同时测定的肌酐清除率未显示异常,但提示庆大霉素存在额外的肾小管分泌,而在健康对照中未见此现象。头孢氨苄、依匹西林和复方新诺明的两种成分口服吸收延迟。头孢氨苄和甲氧苄啶的肾清除率未改变,但依匹西林和磺胺甲恶唑的排泄再次增加。这表现为最大血清浓度(Cmax)延迟和降低,但尿回收率增加。在45至60分钟内静脉输注加倍剂量的庆大霉素,可使血清曲线平稳,大多数常见病原体的MIC值被超过3小时及以上。然而,该建议的临床适用性有待进一步的疗效和安全性研究。