Enhancement of transmucosal permeation of cyclosporine by benzalkonium chloride.
OBJECTIVE
Permeation of cyclosporin A (CsA) through intact and de-epithelialized human vaginal mucosa in the presence and absence of benzalkonium chloride (BZCl) was tested.


METHODS
Human vaginal mucosa (snap-frozen in liquid nitrogen, stored at -85 degrees C) had been used for permeability experiments. CsA permeation through thawed frozen intact and de-epithelialized vaginal mucosa was determined using a flow-through diffusion apparatus (20 degrees C, 24 h). Flux rates for CsA across these two mucosae were determined in the presence and absence of 0.01% BZCl. ANOVA and Duncan's multiple range test were used to test for steady-state and an unpaired t-test with Welch's correction was used to test for differences between the mean flux values at each time point (significance level of 5%). A piece of thawed tissue from each patient, before and after de-epithelialization, was placed in formalin and histologically examined.


RESULTS
Flux rates of CsA across intact vaginal mucosa tended to increase by 28-46% in the presence of 0.01% BZCl, and CsA across de-epithelialized mucosa by approximately 28%. The latter differences were statistically significantly higher after 10 h. Flux rates across de-epithelialized mucosa were 52-140% higher in the presence of 0.01% BZCl (statistically significantly higher after 12 h).


CONCLUSIONS
The permeation of CsA through intact and de-epithelialized human vaginal mucosa can be enhanced by 0.01% BZCl.
Department of Pharmacology, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa. pvdb@sun.ac.za
P
P
van der Bijl
A D
AD
van Eyk
A A
AA
Gareis
I O C
IO
Thompson
D000328:Adult; D000368:Aged; D000465:Algorithms; D000704:Analysis of Variance; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004058:Diffusion; D004347:Drug Interactions; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010539:Permeability / Q000187:drug effects; D013223:Statistics as Topic; D013501:Surface-Active Agents / Q000494:pharmacology*; D014621:Vagina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D001548:Benzalkonium Compounds; D007166:Immunosuppressive Agents; D013501:Surface-Active Agents; D016572:Cyclosporine