Koup J R, Gibaldi M, McNamara P, Hilligoss D M, Colburn W A, Bruck E
Clin Pharmacol Ther. 1978 Nov;24(5):571-5. doi: 10.1002/cpt1978245571.
The effect of chloramphenicol therapy (48 mg/kg/day) on the serum concentrations of phenytoin and phenobarbital was studied in a patient previously stabilized on anticonvulsant medications. Phenytoin, 12 mg/kg/day, and phenobarbital, 5 mg/kg/day resulted in serum concentrations averaging 10.8 microgram/ml before and 30.5 microgram/ml, after chloramphenicol therapy. A reduction in dose of both phenytoin and phenobarbital was required to minimize adverse effects during the course of chloramphenicol therapy. An average daily dose of phenytoin of 9.1 mg/kg resulted in an average serum concentration of 17.8 microgram/ml. A daily dose of phenobarbital of 4.0 mg/kg resulted in an average serum concentration of 37.1 microgram/ml. These changes indicate 50.5% and 40.4% decreases in clearance of phenytoin and phenobarbital. Multiple-dose nonlinear regression analysis of phenytoin and phenobarbital serum concentration data obtained during chloramphenicol therapy indicated a 62.5% and a 29.5% decrease in clearance. Subsequent serum concentration monitoring demonstrated a similar reduction in phenobarbital clearance when chloramphenicol was added to phenobarbital alone.
在一名先前已使用抗惊厥药物稳定病情的患者中，研究了氯霉素治疗（48毫克/千克/天）对苯妥英钠和苯巴比妥血清浓度的影响。在氯霉素治疗前，苯妥英钠剂量为12毫克/千克/天，苯巴比妥剂量为5毫克/千克/天，血清浓度平均为10.8微克/毫升；治疗后，血清浓度平均为30.5微克/毫升。在氯霉素治疗过程中，需要降低苯妥英钠和苯巴比妥的剂量以将不良反应降至最低。苯妥英钠平均每日剂量为9.1毫克/千克时，血清平均浓度为17.8微克/毫升。苯巴比妥每日剂量为4.0毫克/千克时，血清平均浓度为37.1微克/毫升。这些变化表明苯妥英钠和苯巴比妥的清除率分别降低了50.5%和40.4%。对氯霉素治疗期间获得的苯妥英钠和苯巴比妥血清浓度数据进行多剂量非线性回归分析表明，清除率分别降低了62.5%和29.5%。随后的血清浓度监测表明，当仅将氯霉素添加到苯巴比妥治疗中时，苯巴比妥清除率也有类似程度降低。
