Pharmacokinetics of Buprenorphine Hydrochloride (BN·HCl) (2) Role of Stratum Corneum in Percutaneous Absorption of TSN-09 (BN·HCl containing tape) in Male Rats

Abstract

The role of stratum corneum in percutaneous absorption of BN·HCl was investigated (³H-TSN-09 tape; 4×4 cm, BN·HCl content is 20μg/sheet) in a model of normal or damaged skin rats.
1. The microautoradiograms of skin at 8 hr after percutaneous administration of ³H-BN·HCl as a tape formulation (³H-TSN-09) in normal skin rats showed that the radioactivity was predominantly distributed in the stratum corneum.
2. After percutaneous administration of ³H-BN·HCl to damaged skin rats, the radioactivity concentration in the blood reached the C_max at 5 hr and then decreased with the t_1/2 of 5.5 days. And the AUC_0-∞ value was about 4 times higher than that in normal skin rats.
3. After percutaneous administration of ³H-BN·HCl to damaged skin rats, the coefficient of variation of the C_max was about one-third of that in normal skin rats.
4. It was considered that ³H-BN
HCl was mainly absorbed by transcellular route and the stratum corneum played important role in percutaneous absorption of ³H-BN·HCl as evidenced by; i) decreasing the absorption of ³H-BN·HCl and ii) causing inter-individual difference in blood radioactivity.