Fluoroquinolone antibacterial agents are broad spectrum molecules and may be co-prescribed with antimalarial drugs in co-presenting infections. This study aimed at assessing the intestinal permeability of piperaquine (PQ) from dihydroartemisinin-piperaquine (DP) co-formulated antimalarial co-prescribed with ciprofloxacin (CP), using ex vivoabsorption model. Excised intestinal segments (duodenum and ileum) of length 4 cm from New Zealand white albino male rabbits (n=2) loaded with DP suspension equivalent to PQ (100 mg/mL) and CP suspension (100 mg/mL) based on body weights of animals. Similarly, DP alone was loaded to serve as controls C1 and C2, respectively. The organ bath contained Tyrode solution (TS) 100 mL. Sampling (5mL) was taken at 0, 0.5, 1, 2, 4 and 6 h post immersion of tissue. PQ analysis was performed using high pressure chromatographic system with C8 ZorbactEclipse XDB (150 x 4.6 mm, 4.6 µm) column with UV detection at 220 nm and flow rate of 0.7 mL/min. Mobile phase contained acetonitrile: 10 mM ammonium acetate (70: 30 %v/v) and flow rate of 1.0 mL/min at ambient temperature. Area under the curve (AUC) ± SEM at 2 h and 6 h (AUC00-2 and AUC0-6) for tests and their respective control in duodenum were (0.2940±0.1055 versus 0.6198±0.0083 µg.mLh-1, P=0.009) and (1.9270±0.1287 versus 3.3975±0.3638 µg.mLh-1, P=0.006) and ileum (1.5300±0.1242 versus 1.5408±0.4275 µg.mLh-1, P=0.645) and (3.9500±0.0205 versus 5.6603±0.1073 µg.mLh-1, P=0.045), respectively. CP revealed lower permeability indices for PQ in duodenal but not in ileal intestinal barrier. Spacing out of drug regimen may be required for optimum PQ permeation