A Phase 1 pharmacokinetic study of a single-dose bioadhesive clindamycin 2% gel for bacterial vaginosis.

OBJECTIVES: To evaluate pharmacokinetics (PK) of a single dose of an investigational 2% clindamycin phosphate vaginal gel in healthy women by assessment of plasma and vaginal clindamycin concentrations over 7 days, and assess safety. METHODS: Single-centre, Phase 1, single-dose PK study. Blood and vaginal samples were collected daily and safety was evaluated through to Day 7. RESULTS: Twenty-one subjects were enrolled; 20 completed the study. Plasma clindamycin concentrations demonstrated quantifiable values in all subjects through to 24 h post-dose, remaining above the limits of quantification (LOQ) through to 48 h for the majority of subjects. Systemic exposure (AUC0-t) was 1179 (range 62-3822) h·ng/mL. Arithmetic mean AUC0-24 was 818 (range 51-3287) h·ng/mL. Vaginal clindamycin phosphate levels were relatively high 24 h following administration in 15/21 subjects (6 subjects had values >400 µg/g and 9 had values of 100-400 µg/g). The levels dropped in most participants to below the LOQ 2 days following dosing. In a few participants, levels remained elevated for several days. Maximal amounts of vaginal clindamycin occurred on Day 2 with a mean value of 30.3 µg. One treatment-emergent adverse event (TEAE) of moderate-severity headache not related to study drug was reported and resolved on Day 1. No TEAEs were related to physical examinations, pelvic examinations, laboratory values or vital signs. CONCLUSIONS: The vaginal concentrations of clindamycin phosphate plus the clindamycin plasma profile over time are consistent with release of drug from the investigational gel over 24 to 72 h. A single dose was well tolerated.