The Influence of Chitosan on the Oral Bioavailability of Acyclovir—a Comparative Bioavailability Study in Humans

PURPOSE: The effects of chitosan hydrochloride on the oral absorption of acyclovir in humans were studied to confirm the absorption enhancing effects reported for in vitro and rat studies, respectively. METHODS: A controlled, open-label, randomized, 3-phase study was conducted in 12 healthy human volunteers. Zovirax 200 mg dispersible tablets co-administered with doses of 400 and 1000 mg chitosan HCl were compared with Zovirax only. RESULTS: The expected increased absorption of acyclovir was not observed. On the contrary, mean area under the plasma concentration-time curve (AUC0-12 h) and maximal plasma concentration (C(max)) decreased following concomitant chitosan intake (1402 versus 1017 and 982.0 ng∙h/ml and 373 versus 208 and 235 ng/ml, respectively). In addition, T(max) increased significantly in presence of 1000 mg of chitosan from 1 to 2 h. CONCLUSIONS: The results of this study in human volunteers did not confirm an absorption enhancing effect of chitosan. Reference values were comparable to literature data, whereas addition of chitosan resulted in significant opposite effects on C(max), T(max) and AUC. Additional studies are needed to investigate the cause of the discrepancy. The observed variability and complex potential interactions may complicate the use of chitosan HCl in oral pharmaceutical formulations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11095-014-1613-y) contains supplementary material, which is available to authorized users.