Effect of some Artemisinin and Combination Therapy Regimens with and without Concomitant Administration of Phospholipids on the Levels of Plasma Aminotransferases and Bilirubin in Nigerian Male Subjects

Emmanuel I Etim, Etienne E Essien, Olorunfemi A Eseyin, Imo E Udoh

Abstract


Background: Previous studies in animal have shown that high doses of artemisinin caused injury to liver cells. Presently artemisinin and its derivatives such as artesunate (ART), and it’s combination therapy (ACT) has been adopted as the frontline drug for treatment of uncomplicated malaria in Nigeria without considering the effect it has on some major organs of the body.

Objective: The objective of this study was to evaluate the effect of ART when administered as a monotherapeutic agent and in combination as ACT on the plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin (BIL) and the effect of concomitant administration of a hepatotonic phospholipid (PL) on such effects.

Methodology: The prepared plasma samples were analyzed using the end point calorimetric method for each parameter as explained in the Randox kits manual.

Results: Co-administration of ART with amodiaquine (AMQ), mefloquine (MFQ) and sulphadoxine/pyremethamine (SP) respectively, on the 4th day of the studies increased the mean plasma concentration of AST to 80.70%, 108.0% and 75.0% against 59% for ART alone; ALT increased to 104%, 33.0% and 43.30% against 25.05% for ART alone; total bilirubin (TBIL) increased to 80.0%, 78.88% and 98.91% against 17.6% for ART alone. The co-administration and post-administration of ART and the ACTs with 900mg and 1800mg daily dose of PL respectively reduced the levels of the AST, ALT and BIL by 65.0% and 97.0% of the increased values respectively on 4th day.

Discussion: The results suggest that ART as a monotherapeutic agent has injurious effect on the liver, and this effect is aggravated when ART is used in ACTs, however, the co-administration with phospholipids cushions the adverse effects.

Key words: Artesunate; Artemisinin Combination Therapy (ACT); Aminotransferases; Bilirubin; Phospholipids


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