Toxicological fate of Artemether-lumefantrine after exposure to enzyme inducer (Phenobarbitone) and inhibitor (Omeprazole) of Cytochrome P450 in Wister rats

Background: Due to lack of toxicological fate information of artemether-lumefantrine (AL) after exposure to Cytochrome P450 inducer (phenobarbitone) and inhibitor (omeprazole) this research work was undertaken to assess the AL toxicological fate after exposure to phenobarbitone and omeprazole in Wister rats.

Methods: Phenobarbitone (10 mg/kg) and omeprazole (20 mg/kg) were administered orally to albino rats for twenty-eight days. Artemether-lumefantrine was administered on the day 29, 30 and 31. The rats were euthanized under chloroform anesthesia on day 32. Blood samples collected from abdominal aorta were assessed for toxicity markers such as weights, glucose, lipids, renal electrolytes, liver enzymes and hematological indices.

Results: Out of the thirty-seven toxicity markers assessed, twenty-three showed significant differences (P<0.05). Phenobarbitone and omeprazole increased weight significantly after 14 days and 28 days. Phenobarbitone, omeprazole, artemether-lumefantrine, phenobarbitone-artemether-lumefantrine (PAL) and omeprazole-artemether-lumefantrine (OAL) increased weight between day 28 and 32. Glucose was increased by PAL and OAL. Cholesterol, Triglyceride, High Density Lipoprotein and Low-Density Lipoprotein were significantly decreased by PAL and OAL. Except LDL, other lipids were decreased significantly P<0.05 by AL. Urea, creatinine, and chloride ion increased due to AL and PAL, but decreased by OAL. Alkaline phosphatase, conjugated bilirubin and total bilirubin were altered by PAL and OAL. Eleven haematological indices also changed significantly.

Conclusion: Phenobarbitone and omeprazole altered the toxicological potential of artemether-lumefantrine after exposure. Artemether-lumefantrine may be recommended to be used with caution among patients which are chronic users of phenobarbitone in epilepsy and omeprazole in gastric ulcers.