The comparison of tape-stripping and microdialysis in topical pharmacokinetics and bioequivalency studies

The aim of this study was to examine topical bioequivalence (BE) by Microdialysis (MD) and Tape-stripping methods.BE of two commercial oxytetracycline hydrochloride (OTC) formulations were investigated in 12 healthy volunteers. After the application of formulations on forearms, samples were collected at 30-minute intervals upto four hours by DMD. Samples were obtained at 0.25, 0.5, 1, 1.5, 2, 3 ve 4. hours by tape-stripping.The ratio of the areas under the dermis concentration-time profiles (AUCTest/AUCReference) was 2.25±2.16. The bioavailability of the test product was not found to be BE at 90 % CI.Pharmacokinetic modelling of MD data yielded transfer rates from ointment to extracellular compartment (k1) of 6.77±2.45, 26.8±9.40 µg/h; dispositon rate constant (kd) of 16.3±8.4, 26.8±9.4 h-1, skin distribution (Vd) of 173±370, 924±1907 mL for test and reference, respectively.The ratio of the areas under the OTC amount in Stratum Corneum (SC)-time (AUCTest/AUCReference) profiles was found to be 0.838±0.460. The test product was found to be BE as regarding AUC and Cmax at % 90 CI.Dermatopharmacokinetic analysis yielded absorption rate constant (ka) of 2.76±2.91, 9.33±10.10 h-1; disposition rate constant (kd) of 0.167±0.105, 0.244±0.219 h-1; volume of distribution (Vd) of 2.24±1.05, 1.66±0.96 mL; biological half life (t1/2) of 5.47±2.72, 6.53±7.14 h; clearance (CL) of 0.304±0.108, 0.398±0.528 mL/h for test and reference, respectively.The correlation between two methods was weak (r2 = 0.002-0.292).As a result, it was concluded that tape-stripping is a useful method to assess the penetration to SC, however, SC concentration was found not to be a predictive of OTC concentration in the living skin, dermis. Therefore, DMD sampling can better assess the topical BE, measuring the levels of OTC at the site of action.