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邦戈羚羊(Tragelaphus eurycerus isaaci)抗结核药物的群体药代动力学及牛分枝杆菌感染的治疗

Population pharmacokinetics of antituberculous drugs and treatment of Mycobacterium bovis infection in bongo antelope (Tragelaphus eurycerus isaaci).

作者信息

Auclair Barbara, Mikota Susan K, Peloquin Charles A, Aguilar Roberto, Maslow Joel N

机构信息

National Jewish Medical and Research Center, Denver, Colorado 80206, USA.

出版信息

J Zoo Wildl Med. 2002 Sep;33(3):193-203. doi: 10.1638/1042-7260(2002)033[0193:PPOADA]2.0.CO;2.

Abstract

After clinical illness, treatment, and death of a captive male bongo antelope (Tragelaphus eurycerus isaaci) caused by tuberculosis involving Mycobacterium bovis, four tuberculin test reactive captive bongos were treated for 6 mo with isoniazid (INH) and rifampin (RIF) and intermittent single doses of other medications before being euthanized. In all cases, postmortem examination indicated no evidence of active disease and cultures of multiple organs were negative. We present detailed pharmacokinetic (PK) data for amikacin (AMK), ethambutol (EMB), INH, pyrazinamide (PZA), RIF, and levofloxacin in four female bongos. Adequate absorption and serum levels were obtained after parenteral administration of AMK, EMB, and INH and after oral administration of INH and PZA. Parenterally administered drugs were well described by a one-compartment PK model with first-order absorption and elimination processes. Treatment with INH and RIF over a 6-mo period did not result in demonstrable adverse effects. Starting doses of 10-15 mg/kg, i.m., or 30 mg/kg, p.o., of INH, 50 mg/kg, p.o., of EMB, and 25 mg/kg, i.m., s.i.d., of AMK are recommended. The treatment is continued with at least two drugs to which the organism is susceptible for a total treatment length of 6-12 mo. Treatment may be an option to eradicate M. bovis from suspect animals, with carefully administered and monitored drug treatment.

摘要

一只圈养雄性邦戈羚羊(Tragelaphus eurycerus isaaci)因感染牛分枝杆菌导致结核病,出现临床症状、接受治疗后死亡。之后,对4只结核菌素试验呈反应性的圈养邦戈羚羊用异烟肼(INH)和利福平(RIF)治疗6个月,并间歇性单剂量使用其他药物,随后实施安乐死。在所有病例中,尸检均未发现活动性疾病迹象,多个器官的培养结果均为阴性。我们提供了4只雌性邦戈羚羊中阿米卡星(AMK)、乙胺丁醇(EMB)、异烟肼、吡嗪酰胺(PZA)、利福平和左氧氟沙星的详细药代动力学(PK)数据。经肠胃外给予AMK、EMB和INH以及经口服给予INH和PZA后,均实现了充分吸收并达到了血清水平。肠胃外给药的药物可用具有一级吸收和消除过程的单室PK模型很好地描述。6个月期间使用INH和RIF治疗未产生明显不良反应。建议INH的起始剂量为10 - 15mg/kg(肌肉注射)或30mg/kg(口服),EMB为50mg/kg(口服),AMK为25mg/kg(肌肉注射,每日一次)。治疗应持续使用至少两种该病原体敏感的药物,总治疗时长为6 - 12个月。对于疑似感染动物,通过谨慎给药和监测的药物治疗,治疗可能是根除牛分枝杆菌的一种选择。

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