非核苷类逆转录酶抑制剂（依非韦伦和奈韦拉平）对动物模型中格列齐特药效学活性的影响。
Influence of non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine) on the pharmacodynamic activity of gliclazide in animal models.
机构信息
Pharmacology Division, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam-530 003, Andhra Pradesh, India.
出版信息
Diabetol Metab Syndr. 2009 Oct 9;1(1):15. doi: 10.1186/1758-5996-1-15.
BACKGROUND
Type 2 diabetes may occur as a result of HIV infection and/or its treatment. Gliclazide is a widely used drug for the treatment of type 2 diabetes. Efavirenz and nevirapine are widely used non-nucleoside reverse transcriptase inhibitors for the treatment of HIV infection. The role of Efavirenz and nevirapine on the pharmacodynamic activity of gliclazide is not currently known. The objective of this study was to examine the effect of oral administration of efavirenz and nevirapine on blood glucose and investigate their effect on the activity of gliclazide in rats (normal and diabetic) and rabbits to evaluate the safety and effectiveness of the combination.
METHODS
Studies in normal and alloxan induced diabetic rats were conducted with oral doses of 2 mg/kg bd. wt. of gliclazide, 54 mg/kg bd. wt. of efavirenz or 18 mg/kg bd. wt. of nevirapine and their combination with adequate washout periods in between treatments. Studies in normal rabbits were conducted with 5.6 mg/1.5 kg bd. wt. of gliclazide, 42 mg/1.5 kg bd. wt. of efavirenz or 14 mg/1.5 kg bd. wt. of nevirapine and their combination given orally. Blood samples were collected at regular time intervals in rats from retro orbital puncture and by marginal ear vein puncture in rabbits. All the blood samples were analysed for blood glucose by GOD/POD method.
RESULTS
Efavirenz and nevirapine alone have no significant effect on the blood glucose level in rats and rabbits. Gliclazide produced hypoglycaemic/antidiabetic activity in normal and diabetic rats with peak activity at 2 h and 8 h and hypoglycaemic activity in normal rabbits at 3 h. In combination, efavirenz reduced the effect of gliclazide in rats and rabbits, and the reduction was more significant with the single dose administration of efavirenz than multiple dose administration. In combination, nevirapine has no effect on the activity of gliclazide in rats and rabbits.
CONCLUSION
Thus, it can be concluded that the combination of efavirenz and gliclazide may need dose adjustment and care should be taken when the combination is prescribed for their clinical benefit in diabetic patients. The combination of nevirapine and gliclazide was safe. However, further studies are warranted.
背景
2 型糖尿病可能是由 HIV 感染和/或其治疗引起的。格列齐特是一种广泛用于治疗 2 型糖尿病的药物。依非韦伦和奈韦拉平是广泛用于治疗 HIV 感染的非核苷类逆转录酶抑制剂。目前尚不清楚依非韦伦和奈韦拉平对格列齐特药效学活性的影响。本研究旨在研究口服依非韦伦和奈韦拉平对血糖的影响，并探讨其对正常和糖尿病大鼠及家兔格列齐特活性的影响，以评估该联合用药的安全性和有效性。
方法
在正常和四氧嘧啶诱导的糖尿病大鼠中进行了口服剂量为 2mg/kg 体重的格列齐特、54mg/kg 体重的依非韦伦或 18mg/kg 体重的奈韦拉平及其组合治疗的研究，在治疗之间有足够的洗脱期。在正常家兔中进行了 5.6mg/1.5kg 体重的格列齐特、42mg/1.5kg 体重的依非韦伦或 14mg/1.5kg 体重的奈韦拉平及其组合的口服给药研究。从眼眶后穿刺和兔耳缘静脉穿刺定期采集大鼠的血样，所有血样均采用 GOD/POD 法分析血糖。
结果
依非韦伦和奈韦拉平单独使用对大鼠和兔的血糖水平无显著影响。格列齐特在正常和糖尿病大鼠中产生降血糖/抗糖尿病活性，在 2 小时和 8 小时达到峰值，在正常兔中在 3 小时产生降血糖活性。联合使用时，依非韦伦降低了格列齐特在大鼠和兔中的作用，单剂量给药比多剂量给药的降低更为显著。联合使用时，奈韦拉平对大鼠和兔中格列齐特的活性没有影响。
结论
因此，可以得出结论，依非韦伦和格列齐特的联合用药可能需要调整剂量，在为糖尿病患者开具联合用药的临床益处时应谨慎。奈韦拉平与格列齐特联合使用是安全的。然而，还需要进一步的研究。
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