Effect of Co - Administration of Artemether and Nevirapine on Hepato-Renal Functions in Wistar Rats
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Date
2017
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Abstract
Malarial and Human Immuno-deficiency Virus (HIV) infections occur together in many parts of the world creating the need for co-administration of antimalarial and antiretroviral drugs with potential for drug interactions. This study investigated the effect of co-administration of artemether (ART) and nevirapine (NVP) on liver enzymes and kidney functions in both non-immuno-compromised and immuno-compromised Wistar rats. Animals were divided into six (6) groups of 6 rats each. Groups 4, 5 and 6 received 30 mg/kg NVP daily for 21 days. Groups 1, 2 and 3 received 3%v/v Tween 80 (T80) from days 1-21; and in addition groups 2 and 3 received 5 mg/kg ART (ART5) and 10 mg/kg ART (ART10) respectively from days 15-21. Groups 5 and 6 also received ART5 and ART10 respectively in addition to NVP from days 15 to 21 and all drugs were administered intraperitoneally. On day 22, animals were sacrificed and sera obtained. Alanine transaminase (ALT), alkaline phosphatase (ALP) and aspartate transaminase (AST) were determined using standard kinetic methods. Total protein, albumin, creatinine and urea levels were determined using enzyme selectra XL machine. In a separate experiment, the above protocol was repeated in rats administered (immuno-compromised) with dexamethasone 20 mg/kg on day 1 followed by booster doses of 10 and 5 mg/kg on days 8 and 15 respectively. Statistically significant increases (p<0.05) in ALP and ALT were observed in NVP alone and NVP-ART10 groups in both non-immuno-compromised and immuno-compromised rats respectively. In immuno-compromised rats, significant increase (p<0.05) in ALP was also observed in NVP-ART10 group. No changes were observed in total protein, albumin and urea in both groups. However, a significant increase (p<0.05) in creatinine was observed in NVP-ART10 administered group in both non-immuno-compromised and immunocompromised rats. Alterations in ALP, ALT and creatinine observed suggest impairment in normal liver and kidney functions, hence the need for precautionary measures when ART and NVP are co-administered.
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Keywords
Artemether, Nevirapine, Co-administration, Kidney function, Liver enzymes