Improving the pharmacokinetic and pharmacodynamic properties of a drug by chemical conversion to a chimera drug.
The purpose of the present study is to investigate a new concept which involves the conjugation of two drugs having different pharmacological activities which is termed a 'chimera drug (mutual prodrug)', in drug delivery optimization using a chemical modification approach. The conjugates of FP, an NSAID, with histamine H(2) antagonists were synthesized, in order to investigate the reduction in gastric damage by NSAID, and their pharmaceutical, pharmacokinetic and pharmacological properties were examined. The limited data obtained herein indicate that the chimera drug composed of FP and PPA was effective in reducing gastric damage by FP, with no changes in its biopharmaceutical properties, compared with the conventional prodrugs such as ester-type prodrugs.
Otagiri
M
M
Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, Japan. otagirim@gpo.kumamoto-u.ac.jp
Imai
T
T
Fukuhara
A
A
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000494:pharmacology*; D005480:Flurbiprofen / Q000493:pharmacokinetics / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000378:metabolism; D006868:Hydrolysis; D016014:Linear Models; D008297:Male; D011355:Prodrugs / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006635:Histamine H2 Antagonists; D011355:Prodrugs; D011993:Recombinant Fusion Proteins; D005480:Flurbiprofen