Effect of Short-Term Concomitant Use of Polyherbal Mixture on the Bioavailability of HIV Protease Inhibitors and Organ Damage in Rats
http://www.doi.org/10.26538/tjnpr/v1i4.5
Keywords:
Protease inhibitors,, Pharmaceutical availability,, Polyherbal formulations,, Antiretrovirals.Abstract
Many herbal remedies are used as complementary therapy to combination antiretroviral therapy (cART). Contrary to the general assumptions that herbal remedies are harmless because of the natural source, many have been found to be toxic. This study seeks to assess the effect of concomitant administration of HIV protease inhibitors (PIs) Atazanavir/ritonavir (Atz/r) and Lopinavir /ritonavir (Lpv/r) with marketed poly-herbal mixture “Goko cleanser herbal mixture (GCHM)”. A modified in vitro study of the release profile of Atz/r and Lpv/r was evaluated using dissolution apparatus II. A 15-day sub-acute toxicity test was carried out with GCHM administered orally at 0.5 mL/kg and 1.5 mL/kg simulating low and high doses, respectively together with either Atz/r (10 mg/kg b.wt) or Lpv/r (5 mg/kg b.wt) to 4-week old Wistar rats. Histopathology of the heart and liver, haematological and biochemical analyses of blood obtained via cardiac puncture was carried out. The presence of the poly herbal formulation reduced the release of both PIs in vitro irrespective of the media used. There was a significant decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P < 0.05) at a dose of 1.5 mL/kg GCHM compared to the control. Photomicrographs of the liver showed evidence of
enlarged nuclei and degenerated hepatocytes in the high dose group treated with Atz/r / GCHM. Concomitant administration of the poly-herbal formulation GCHM, alongside PIs adversely affected pharmaceutical availability which may influence the bioavailability of the PIs.
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