Adebayo G I, Mabadeje A F
Department of Pharmacology, College of Medicine, Lagos, Nigeria.
Aliment Pharmacol Ther. 1988 Aug;2(4):341-6. doi: 10.1111/j.1365-2036.1988.tb00706.x.
On the basis of the report that benzimidazoles bind to and inhibit the hepatic cytochrome P-450 enzyme system, the effect of mebendazole and albendazole on theophylline disposition was studied in 12 volunteers. Mebendazole at a dose of 100 mg b.d. for 3 days did not significantly alter the theophylline half-life, volume of distribution or clearance in a group of six. In another group of six adult volunteers, albendazole (400 mg) pretreatment did not alter the same parameters. However, in this second group, pretreatment with cimetidine (400 mg t.d.s. for 5 days) significantly increased theophylline half life from 7.7 to 9.8 +/- 1.5 h (P less than 0.001) and reduced its clearance from 0.8 to 0.60 +/- 0.1 ml min-1 kg-1 (P less than 0.005). The volume of distribution was not altered significantly. It is concluded that at therapeutic doses it is unlikely that mebendazole or albendazole will induce theophylline toxicity if co-administered with the bronchodilator. Cimetidine-induced impairment of theophylline metabolism is such that toxicity will be more likely in individuals with initial high theophylline clearance.
基于苯并咪唑类药物可结合并抑制肝细胞色素P - 450酶系统的报道，在12名志愿者中研究了甲苯达唑和阿苯达唑对茶碱代谢的影响。一组6名志愿者服用剂量为每日100mg、连服3天的甲苯达唑后，茶碱的半衰期、分布容积或清除率均未出现显著改变。在另一组6名成年志愿者中，阿苯达唑（400mg）预处理后上述参数也未改变。然而，在这第二组中，西咪替丁（每日400mg，分三次服用，连服5天）预处理使茶碱半衰期从7.7小时显著延长至9.8±1.5小时（P<0.001），清除率从0.8降至0.60±0.1ml·min⁻¹·kg⁻¹（P<0.005），分布容积未出现显著改变。研究得出结论，治疗剂量下，甲苯达唑或阿苯达唑与支气管扩张剂合用时不太可能引发茶碱中毒。西咪替丁引起的茶碱代谢损伤使得初始茶碱清除率较高的个体更易出现中毒。
