Effect of molecular weight on the dermatopharmacokinetics and systemic disposition of drugs after intracutaneous injection.
The aim of this study was to investigate the effect of molecular weight on the topical migration and systemic absorption of drugs, sodium salicylate (SA), calcein sodium (CAL) and FITC-dextrans (FD-4, FD-10, FD-20 and FD-40), after intracutaneous (i.c.) injection. The apparent diffusion coefficients in the skin (D(s)) of SA, CAL and FD-4 after i.c. injection were almost the same and slightly less than 1x10(-4)cm(2)/min. The D(s) value drastically decreased with molecular weight more than 10kDa. The plasma concentration-time curve after i.c. injection was predicted by the convolution method. The ratio of AUC (observed/predicted) was approximately unity for SA, CAL and FD-4 although the systemic absorption of only FD-4 was delayed. In contrast, the AUC ratios of FD-10, FD-20 and FD-40 were about 0.5, 0.2 and 0.06, respectively, and obviously decreased with the molecular weight. The elimination of FD-10, FD-20 and FD-40 from the skin was slow and the drugs tended to remain in the muscle. These results indicated the importance of diffusion in the skin and permeability through the blood vessels for local migration and systemic absorption of drugs after penetration into viable skin.
Yoshida
Daisuke
D
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
Todo
Hiroaki
H
Hasegawa
Tetsuya
T
Sugibayashi
Kenji
K
D000465:Algorithms; D000818:Animals; D004058:Diffusion; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D010599:Pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D014018:Tissue Distribution
D004364:Pharmaceutical Preparations