Chemistry:Target-mediated drug disposition

From HandWiki
Short description: Process


Target-mediated drug disposition (TMDD), is the process in which a drug binds with high affinity to its pharmacological target (for example, a receptor) to such an extent that this affects its pharmacokinetic characteristics. Various drug classes can exhibit TMDD, most often these are large compounds (biologics such as antibodies, cytokines or growth factors[1]) but also smaller compounds can exhibit TMDD (such as warfarin). A typical TMDD pattern of antibodies displays non-linear clearance and can be seen at concentration ranges that are usually defined as 'mid-to-low'. In this concentration range, the target is partly saturated.[2][3]

References

  1. Berends, Sophie E.; van Steeg, Tamara J.; Ahsman, Maurice J.; Singh, Sharat; Brandse, Johannan F.; D’Haens, Geert R. A. M.; Mathôt, Ron A. A. (December 2019). "Tumor necrosis factor-mediated disposition of infliximab in ulcerative colitis patients" (in en). Journal of Pharmacokinetics and Pharmacodynamics 46 (6): 543–551. doi:10.1007/s10928-019-09652-5. ISSN 1567-567X. PMID 31489538. 
  2. Dua, P; Hawkins, E; van der Graaf, Ph (2015-04-10). "A Tutorial on Target-Mediated Drug Disposition (TMDD) Models: A Tutorial on Target-Mediated Drug Disposition (TMDD) Models" (in en). CPT: Pharmacometrics & Systems Pharmacology 4 (6): 324–337. doi:10.1002/psp4.41. PMID 26225261. 
  3. An, Guohua (February 2020). "Concept of Pharmacologic Target‐Mediated Drug Disposition in Large‐Molecule and Small‐Molecule Compounds" (in en). The Journal of Clinical Pharmacology 60 (2): 149–163. doi:10.1002/jcph.1545. ISSN 0091-2700. PMID 31793004.