Stereoselective behavior of a novel biodegradable racemic ketoprofen injectable implant in rats.
The stereoselectivity of release of ketoprofen (KET) enantiomers from a biodegradable injectable implant containing racemic KET (rac-KET) was investigated in vivo. A pre-column chiral derivatization RP-HPLC method was employed to assay diastereoisomeric derivatives of R- and S-KET. The rac-KET injectable implant, once injected subcutaneously in rats, produced long-lasting plasma levels of S-KET, which were always greater than those of R-KET. The difference in enantiomer concentration was to be related to stereoselective release, due to stereoselective interaction between D,L-PLG in the implant and KET enantiomers, as well as the chiral inversion of KET in vivo. The rac-KET injectable implant provided the sustained release of S-KET with effective plasma levels maintained for about 8 wk after a single injection.
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310031, People's Republic of China.
Sheng-Hao
SH
Wang
Li-Na
LN
Yin
Ze-Hua
ZH
Liang
Si-Jie
SJ
Lu
Su
S
Zeng
D020341:Absorbable Implants; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004343:Drug Implants; D007279:Injections, Subcutaneous; D007660:Ketoprofen / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D011091:Polyesters; D011760:Pyrrolidinones; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D004343:Drug Implants; C523727:N-ethyl-2-pyrrolidone; D011091:Polyesters; D011760:Pyrrolidinones; C033616:poly(lactide); D007660:Ketoprofen