Konstan M W, Hoppel C L, Chai B L, Davis P B
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio.
J Pediatr. 1991 Jun;118(6):956-64. doi: 10.1016/s0022-3476(05)82218-8.
Antiinflammatory therapy with ibuprofen has been proposed to retard the progression of lund disease in cystic fibrosis (CF). The pharmacokinetics and toxicity of ibuprofen were investigated in a randomized, double-blind, placebo-controlled, 3-month dose-escalation study in 19 children with CF, 6 to 12 years of age. The subjects received orally and twice daily 300 mg of drug during the first month, 400 mg in the second month, and 600 mg in the third month. Ibuprofen pharmacokinetics and evaluation for adverse effects were performed at the beginning and end of each month. The dose of ibuprofen was increased if peak plasma concentration (Cmax) was less than 50 micrograms/ml. To preserve the blind nature of the study, the dose in matched subjects taking placebo was also increased. The subjects randomly assigned to receive ibuprofen (n = 13) completed 26 months of treatment; placebo subjects (n = 5) completed 12 months. With dose escalation, Cmax and the area under the concentration-time curve from zero to infinity significantly increased (p less than 0.01). The pharmacokinetics of ibuprofen in 13 children with CF who received 13.4 +/- 4.1 mg/kg (mean +/- SD) were compared with those in four healthy children who received a similar dose. Peak plasma concentration (48 +/- 17 micrograms/ml) was decreased by 27% (p = 0.06), the area under the concentration-time curve (6.1 +/- 1.7 mg.min/ml) was decreased by 46% (p less than 0.001), apparent total clearance (2.3 +/- 0.6 ml/min.kg-1) was increased by 77% (p less than 0.01), and apparent volume of distribution during terminal phase (291 +/- 91 ml/kg) was increased by 84% (p = 0.01) in the children with CF. Time to Cmax (66 +/- 20 minutes) and elimination half-life (92 +/- 27 minutes) were not significantly different. No subjects were withdrawn from the study because of side effects. No adverse effects could be attributed to ibuprofen. Thus ibuprofen administration has no significant toxic effects, but Cmax will need to be monitored for effective dosing in patients with CF.
有人提出用布洛芬进行抗炎治疗以延缓囊性纤维化（CF）患者隆德病的进展。在一项针对19名6至12岁CF儿童的随机、双盲、安慰剂对照、为期3个月的剂量递增研究中，对布洛芬的药代动力学和毒性进行了研究。受试者在第一个月口服药物，每日两次，每次300毫克；第二个月为400毫克；第三个月为600毫克。在每个月的开始和结束时进行布洛芬药代动力学和不良反应评估。如果血浆峰浓度（Cmax）低于50微克/毫升，则增加布洛芬剂量。为保持研究的盲法性质，服用安慰剂的匹配受试者的剂量也相应增加。随机分配接受布洛芬治疗的受试者（n = 13）完成了26个月的治疗；安慰剂组受试者（n = 5）完成了12个月的治疗。随着剂量递增，Cmax以及从零到无穷大的浓度-时间曲线下面积显著增加（p < 0.01）。将13名接受13.4±4.1毫克/千克（均值±标准差）布洛芬治疗的CF儿童的药代动力学与4名接受相似剂量的健康儿童的药代动力学进行比较。CF儿童的血浆峰浓度（48±17微克/毫升）降低了27%（p = 0.06），浓度-时间曲线下面积（6.1±1.7毫克·分钟/毫升）降低了46%（p < 0.001），表观总清除率（2.3±0.6毫升/分钟·千克⁻¹）增加了77%（p < 0.01），终末相表观分布容积（291±91毫升/千克）增加了84%（p = 0.01）。达峰时间（66±20分钟）和消除半衰期（92±27分钟）无显著差异。没有受试者因副作用退出研究。没有不良反应可归因于布洛芬。因此，服用布洛芬没有明显的毒性作用，但对于CF患者，为了有效给药需要监测Cmax。
