Enhancing effect of Labrasol on the intestinal absorption of ganciclovir in rats

Abstract

Ganciclovir (GCV), like other nucleoside analogs such as trifluridine and acyclovir (ACV), is hydrophilic, poorly permeable across membranes and orally low-bioavailable. In the present studies, Labrasol was evaluated for improving intestinal absorption of GCV through in vitro and in vivo experiments. The effect of Labrasol on absorption of GCV in rat small intestine was investigated using an in situ single-pass perfusion technique. The apparent absorptive clearance (PeA) of GCV with Labrasol in the duodenum, jejunum and ileum was 1.01, 1.28, and 1.49 mL/min/cm (n = 6), respectively, and significant regional differences of GCV absorption among the three segments were observed (p jejunum (p duodenum (p > 0.05). The effects of EDTA, verapamil on the permeability of GCV were conducted. The permeability of GCV was increased by EDTA, verapamil, respectively. The results indicated that paracellular absorption and efflux played important roles in GCV absorption. In vivo absorption GCV in rats was conducted. When GCV at 1 mg/kg dose was administered with Labrasol (10%, v/v), the mean AUC of was determined as 14.45 ± 3.88 μg*h/mL, compared to 8.05 ± 1.52 µg*h/mL without Labrasol. Based on the results, we could conclude that the absorption of GCV through GI lumen would be enhanced by Labrasol. The effect of Labrasol maybe ascribed to both (i) inhibit efflux of GCV from the enterocytes to the GI lumen; and (ii) enhance GCV absorption from the GI lumen through paracellular pathway.

Keywords::

• Ganciclovir
• Labrasol
• paracellular absorption
• P-glycoprotein inhibition
• apparent absorptive clearance