Comparative Analysis of In Vitro Permeation and Human Pharmacokinetic Data for a Bioadhesive Vaginal Tablet as a Potential Clinical Approach for Bacterial Vaginosis.

Background/Objectives: Reformulating oral drugs for vaginal delivery is a current therapeutic strategy for genitourinary tract infections. Bioadhesive delivery systems, by interacting with the mucosal epithelium, improve drug deposition at the application site and are promising carriers for drugs with poor bioavailability. This study compares an in vitro permeation test (IVPT) in excised human vaginal epithelium and a first-in-human (FIH) pharmacokinetic (PK) study for a bioadhesive vaginal tablet developed as a potential clinical approach for bacterial vaginosis (BV). Methods: A Phase 1, single-dose, open-label, crossover study in 24 healthy volunteers evaluated PK differences after ascending doses of the vaginal tablet and an oral comparator, with a 7-day wash-out between administrations. The IVPT examined drug permeation and deposition in excised human vaginal epithelium for the pure drug and drug-loaded tablet. Results: IVPT showed limited penetration of the antimicrobial agent across human vaginal epithelium. Tablet excipients reduced drug accumulation in the ectocervical tissue, further hindering absorption. Single vaginal administration resulted in low plasma drug levels (Cmax 0.084-0.127 ng/mL), irrespective of dose. Mean AUC(0-t) after vaginal tablet administration did not exceed 1.560 h·ng/mL (100 mg) and was significantly lower than for the oral comparator (824.147 h·ng/mL, 100 mg). The IVPT data with human vaginal epithelium supported the FIH data, demonstrating low systemic absorption following single-dose vaginal application and potential for local drug performance. Conclusions: A single dose of the bioadhesive vaginal tablet appears to be a potentially safe alternative for BV treatment, with minimal systemic drug exposure, supporting further research on clinical efficacy and local pharmacodynamics of bioadhesive tablets for BV.