Modulation of ganciclovir intestinal absorption in presence of absorption enhancers.
The purpose of this investigation was to study the influences of absorption enhancers in increasing oral bioavailability of Ganciclovir (GAN) by assessing the transepithelial permeation across cell monolayers in vitro and bioavailability in rats in vivo. The permeation of GAN across Caco-2 and MDCK cell monolayers in the absence/presence of dimethyl-beta-cyclodextrin (DMbetaCD), chitosan hydrochloride (CH), sodium lauryl sulphate (SLS), and their combinations was studied for a 2-h period. GAN was administered to rats in absence/presence of absorption enhancers and drug contents in plasma were estimated. We found that the apparent permeability coefficient (Papp) of GAN in absence of absorption enhancers (control) were 0.261 +/- 0.072 x 10(-6) and 0.486 +/- 0.063 x 10(-6) cm/s in Caco-2 and MDCK cell monolayers, respectively, whereas in the presence of DMbetaCD, CH, SLS, and their combinations, Papp of GAN increased by 5- to 25-fold and 7- to 33-fold as compared to control in Caco-2 and MDCK cell monolayers, respectively. However, in rats, the maximum enhancement in bioavailability of GAN during coadministration of these absorption enhancers was only fivefold compared to GAN control. To conclude, the absorption enhancers-DMbetaCD, CH, SLS, and their combinations demonstrated significant improvement in transepithelial permeation and bioavailability of GAN.
Shah
Pranav
P
Department of Pharmacy, Faculty of Technology & Engineering, The Maharaja Sayajirao University of Baroda, P.O. Box 51, Kalabhavan, Vadodara 390 001, India.
Jogani
Viral
V
Mishra
Pushpa
P
Mishra
Anil Kumar
AK
Bagchi
Tamishraha
T
Misra
Ambikanandan
A
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D004285:Dogs; D017097:Electric Impedance; D015774:Ganciclovir / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000378:metabolism; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000998:Antiviral Agents; D015609:Organotechnetium Compounds; D013501:Surface-Active Agents; D047392:beta-Cyclodextrins; C059584:technetium Tc 99m mannitol; D012967:Sodium Dodecyl Sulfate; D008353:Mannitol; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D048271:Chitosan; D015774:Ganciclovir