Papich Mark G
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA.
Parasit Vectors. 2017 Nov 9;10(Suppl 2):493. doi: 10.1186/s13071-017-2449-1.
Doxycycline has been considered the first drug of choice for treating Wolbachia, a member of the Rickettsiaceae, which has a symbiotic relationship with filarial worms, including heartworms. Wolbachia, is susceptible to tetracyclines, which have been used as adjunctive treatments for heartworm disease. Treatment with doxycycline reduces Wolbachia numbers in all stages of heartworms and improves outcomes and decreased microfilaremia in dogs treated for heartworm disease. The American Heartworm Society recommends treatment with doxycycline in dogs diagnosed with heartworm disease at a dose of 10 mg/kg twice daily for 28 days. If doxycycline is not available, minocycline can be considered as a substitute. However, minocycline has not undergone an evaluation in dogs with heartworm disease, nor has an effective dose been established. Minocycline is an attractive option because of the higher cost of doxycycline and new pharmacokinetic information for dogs that provides guidance for appropriate dosage regimens to achieve pharmacokinetic-pharmacodynamic (PK-PD) targets.
Published reports from the Anti-Wolbachia Consortium (A-WOL) indicate superior in vitro activity of minocycline over doxycycline. Studies performed in mouse models to measure anti-Wolbachia activity showed that minocycline was 1.7 times more effective than doxycycline, despite a 3-fold lower pharmacokinetic exposure. To achieve the same exposure as achieved in the mouse infection model, a pharmacokinetic-pharmacodynamic (PK-PD) analysis was conducted to determine optimal dosages for dogs. The analysis showed that an oral minocycline dose of 3.75 to 5 mg/kg administered twice daily would attain similar targets as observed in mice and predicted for human infections.
There are potentially several advantages for use of minocycline in animals. It is well absorbed from oral administration, it has less protein binding than doxycycline (65% vs 92%) allowing for better distribution into tissue, and it is approximately two times more lipophilic than doxycycline, which may result in better intracellular penetration. More work is needed to document efficacy of minocycline for treating canine heartworm disease.
强力霉素一直被认为是治疗立克次氏体科成员沃尔巴克氏体的首选药物，该菌与包括犬心丝虫在内的丝虫存在共生关系。沃尔巴克氏体对四环素敏感，四环素已被用作犬心丝虫病的辅助治疗药物。用强力霉素治疗可减少犬心丝虫各阶段的沃尔巴克氏体数量，改善治疗效果，并降低犬心丝虫病治疗犬的微丝蚴血症。美国心丝虫协会建议，对诊断为犬心丝虫病的犬使用强力霉素治疗，剂量为10毫克/千克，每日两次，共28天。如果没有强力霉素，米诺环素可被视为替代品。然而，米诺环素尚未在患有犬心丝虫病的犬身上进行评估，也未确定有效剂量。由于强力霉素成本较高，且有关于犬的新的药代动力学信息可为实现药代动力学-药效学（PK-PD）目标的适当给药方案提供指导，米诺环素是一个有吸引力的选择。
抗沃尔巴克氏体联盟（A-WOL）发表的报告表明，米诺环素在体外的活性优于强力霉素。在小鼠模型中进行的测量抗沃尔巴克氏体活性的研究表明，尽管米诺环素的药代动力学暴露量低3倍，但其效果比强力霉素高1.7倍。为了达到与小鼠感染模型相同的暴露量，进行了药代动力学-药效学（PK-PD）分析以确定犬的最佳剂量。分析表明，口服米诺环素剂量为3.75至5毫克/千克，每日两次，将达到与小鼠观察到的以及预测的人类感染相似的目标。
在动物中使用米诺环素可能有几个优点。它口服吸收良好，与强力霉素相比蛋白结合率较低（分别为65%和92%），从而能更好地分布到组织中，并且其亲脂性比强力霉素高约两倍，这可能导致更好的细胞内渗透。需要更多工作来证明米诺环素治疗犬心丝虫病的疗效。
