EX-VIVO PERMEABILITY STUDIES OF DIHYDROARTEMISININ-PIPERAQUINE ANTIMALARIAL IN THE PRESENCE OF FOOD COMPONENTS

Sunday O. Awofisayo*, Ekpedeme Ndem Essien and Ayodeji Akeem Agboke

ABSTRACT

The work was aimed at assessing the interactions between dihydroartemisinin-piperaquine (DP) with food components. Food components [i.e., albumin (ALB), starch (STC) and sunflower oil (SFO)] were co-loaded simultaneously with DP in excised intestinal tissues (i.e., duodenum and ileum) from New Zealand white albino male rabbits. Loaded tissues were submerged in 100 mL Tyrode solution (TS) in organ bath. DP equivalent to (100 mg/mL) of PQ was similarly loaded in duodenum and ileum as controls (CRT1 and CRT2), respectively. Sampling (5mL) was performed from organ bath at timed interval post immersion. Analysis was done using Chemstation high pressure chromatographic reverse-phase (HPLC-RP) system with Zorbact XDB C8 column and mobile phase acetonitrile: 10 mM ammonium acetate (70: 30, %v/v). The wavelength of UV detection was at 220 nm and flow rate 0.7 mL/min. PQ permeation kinetics was zero order in the presence of food components. SFO treatment revealed significant reduction in Cmax in duodenum (0.2951 versus 0.9800 μg/mL) and ileum (0.6150 versus 1.2170 μg/mL), p<0.05. ALB produced no significant difference in Peff disappearance from lumen and Peff appearance in the Tyrode solution for duodenum but higher values for ileum (p<0.05). There was higher rate for appearance (Ka) of PQ in organ bath for STC and SFO treatments in both intestinal segments, p<0.05. Similarly, the extents of permeation at 6 h (AUC6) for the treatments were lower in duodenum than the control. ALB, SFO and STC significantly affected the rate and extent of permeation of PQ across the absorptive intestinal membrane.

Keywords: Food components, Dihydroartemisinin-piperaquine, Intestinal membrane, Permeability, Antimalarial, Drug-drug interaction.