Prediction of clinical effects of infliximab administered for inflammatory bowel disease based on pharmacokinetic and pharmacodynamic modeling.
Biopharm Drug Dispos. 2019 Jun 30;:
Authors: Kimura K, Yoshida A, Katagiri F, Takayanagi R, Yamada Y
Infliximab (IFX) is used as a therapeutic agent for ulcerative colitis (UC) and Crohn’s disease (CD). Although the dosage regimen has been established through clinical trial experience, that has yet to be assessed with a pharmacokinetic and pharmacodynamic model. In the present study, we analyzed sequential changes of clinical response in UC and CD patients following repeated administrations of IFX using the pharmacokinetic/pharmacodynamic model. In addition, we evaluated the presently used dosage regimen for UC patients, as well as potential efficacy gained by increasing the dose and/or reducing the interval of administration for CD patients. Furthermore, we investigated the possibility of evaluating the difference between both diseases in regard to the efficacy of IFX. Sequential changes of clinical response values obtained with our model were in good agreement with observed values following administration of IFX for UC and CD. Our results showed the importance of a loading dose for UC patients, as well as the efficacy of increasing the dose and reducing the interval for CD patients. Also, the efficacy of IFX for both diseases is suggested to be similar. In conclusion, our results show a possible modeling scenario that can accommodate clinical response to IFX administered for UC and CD. Furthermore, they provide confirmation for the present dosage regimens given for these diseases.
PMID: 31256430 [PubMed – as supplied by publisher]