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 invo lves the conjugation of two drugs having different pharmacological activiti es which is termed a 'chimera drug (mutual prodrug)', in drug delivery opti mization using a chemical modification approach. The conjugates of FP, an N SAID, with histamine H-2 antagonists were synthesized, in order to investig ate the reduction in gastric damage by NSAID, and their pharmaceutical, pha rmacokinetic 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 biopharm aceutical properties, compared with the conventional prodrugs such as ester -type prodrugs. (C) 1999 Elsevier Science B.V. All rights reserved.