Touw D J
University Hospital Vrije Universiteit, Department of Pharmacy, Amsterdam, The Netherlands.
Pharm World Sci. 1998 Aug;20(4):149-60. doi: 10.1023/a:1008634911114.
The disposition of many drugs in cystic fibrosis is abnormal compared with healthy individuals. In general, changes include an increased volume of distribution expressed in liters per kg bodyweight for highly hydrophilic drugs such as aminoglycosides, and, to a lesser extent, for penicillins and cephalosporins, together with an increased total body clearance. The main reason for the increased volume of distribution is the increased amount of lean tissue per kg bodyweight, since patients with CF are generally undernourished and have a paucity of adipose tissue. The reason for the increased renal clearance is less clear. Increased glomerular filtration and tubular secretion have been observed. Protein binding generally is unaltered in CF. The fluorquinolones and vancomycin show no altered pharmacokinetics in CF although gastro-intestinal absorption may be delayed for fluorquinolones. Sulphamethoxazole shows increased clearance due to an increased acetylation and, in the case of trimethoprim, renal clearance is increased compared with healthy individuals. As a consequence, drugs that show increased clearance, will lead to reduced serum concentrations and smaller AUCs and therefore CF patients require larger doses per kg bodyweight.
与健康个体相比，囊性纤维化患者体内许多药物的处置情况异常。一般来说，变化包括分布容积增加，对于高度亲水性药物（如氨基糖苷类），以每千克体重升数表示的分布容积增加，对于青霉素和头孢菌素，程度稍轻，同时总体清除率增加。分布容积增加的主要原因是每千克体重瘦组织量增加，因为囊性纤维化患者通常营养不良且脂肪组织较少。肾清除率增加的原因尚不清楚。已观察到肾小球滤过和肾小管分泌增加。囊性纤维化患者的蛋白结合一般未改变。氟喹诺酮类和万古霉素在囊性纤维化患者中的药代动力学未改变，尽管氟喹诺酮类的胃肠道吸收可能延迟。磺胺甲恶唑由于乙酰化增加而清除率增加，对于甲氧苄啶，与健康个体相比，其肾清除率增加。因此，清除率增加的药物会导致血清浓度降低和曲线下面积减小，因此囊性纤维化患者每千克体重需要更大剂量。
