The study assessed intestinal permeability of piperaquine (PQ) from dihydroartemisinin-piperaquine (DP) antimalarial in the presence of lamivudine (LMV). Excised tissues (duodenum and ileum) from New Zealand male albino rabbits (n=2) were loaded with suspension of DP equivalent to PQ (100 mg/mL) and LMV (100 mg/mL) and submerged in Tyrode solution (TS). DP suspension was similarly loaded as control. Sampling (5 mL) of TS was done post immersion of tissues and analyzed for PQ permeation using high pressure liquid chromatographic system. LMV caused a significant increase in PQ permeation across the intestinal membranes. The rate constant (Ka) appearance in organ bath were (0.2457±0.0040 versus 0.0367±0.0008 h-1, P=0.010) for duodenum and (0.2428±0.0006 versus 0.0327±0.0021 h-1, P=0.008) for ileum. The Ka disappearance of PQ were (1.0121±0.0013 versus 0.7600± 0.0008 h-1, P=0.001) from duodenum and (1.0092±0.0003 versus 0.7340±0.0072 h-1, P=0.017) from ileum. Area under the curve at 6 h (AUC6) were (1.2868±0.6725 versus 3.3975±0.3638 µg.mLh-1, P=0.034) for duodenum and (0.7425±0.0089 versus 5.6603±0.1073 µg.mLh-1, P=0.013) for ileum. Co-loading of LMV with DP ex vivo caused significant uptake from the lumen but significant reduction in PQ permeation across the intestinal regions into the organ bath. This may be of biopharmaceutical implication requiring dosage adjustments.
Key words: Dihydroartemisinin-piperaquine, Piperaquine, Lamivudine, Permeability, Intestinal membrane
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