Drug Development and Drug Interactions: Possible Models for Decision-Making
Drug Development and Drug Interactions: Possible Models for Decision-Making
- Possible Model for Decision Making: Metabolism-Based Drug-Drug Interaction Studies (Figures 1-4).
- Possible Model for Decision Making: Transporter-Based Drug-Drug Interaction Studies (Figure 5)
- Possible Models for Determining When In Vivo Transporter-Mediated Drug Interaction Studies Are Needed (Figures 6-11)
- Possible Model for Decision Making: Therapeutic Protein-Drug Interactions (Figure 12).
Figures
Figure 1. Metabolism-Based Drug-Drug Interaction Studies — Decision Tree (PDF - 28KB)- Figure 2. Evaluation of Investigational Drugs as UGT Substrates (PDF - 13KB)
- Figure 3. General Scheme of Model-Based Prediction: The Investigational Drug (and Metabolite Present at ≥25% of Parent Drug AUC) as an Interacting Drug of CYP Enzymes (PDF - 74KB)
- Figure 4. Using a PBPK Model to Explore Drug-Drug Interaction Potential Between a Substrate Drug and an Interacting Drug (PDF - 27KB)
- Figure 5. Evaluation of Investigational Drugs (NME) as Substrates for P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, and OCT2 Transporters (PDF - 16KB)
Figure 6: Decision tree to determine whether an investigational drug is a substrate for P-gp and when an in vivo clinical study is needed. A similar model can be applied to a BCRP substrate —(Modified From Figures in Giacomini KM, et al, Nat. Rev Drug Discov. 9: 215-236, 2010) (PDF - 85KB)Figure 7: Decision tree to determine whether an investigational drug is an inhibitor of P-gp and when an in vivo clinical study is needed. A similar model can be applied to a BCRP inhibitor) — (Modified From Figures in Giacomini KM, et al, Nat. Rev Drug Discov. 9: 215-236, 2010) (PDF - 44KB)Figure 8: Decision tree to determine whether an investigational drug is a substrate for OATP1B1 or OATP1B3 and when an in vivo clinical study is needed— (Modified From Figures in Giacomini KM, et al, Nat. Rev Drug Discov. 9: 215-236, 2010) (PDF - 65KB)Figure 9: Decision tree to determine whether an investigational drug is an inhibitor of OATP1B1 or OATP1B3 and when an in vivo clinical study is needed —(Modified From Figures in Giacomini KM, et al, Nat. Rev Drug Discov. 9: 215-236, 2010) (PDF - 45KB)Figure 10: Decision tree to determine whether an investigational drug is a substrate for OCT2, OAT1, or OAT3 and when an in vivo clinical study is needed —(Modified From Figures in Giacomini KM, et al, Nat. Rev Drug Discov. 9: 215-236, 2010) (PDF - 72KB)Figure 11: Decision tree to determine whether an investigational drug is an inhibitor of OCT2, OAT1, or OAT3 and when an in vivo clinical study is needed — (Modified From Figures in Giacomini KM, et al, Nat. Rev Drug Discov. 9: 215-236, 2010) (PDF - 76KB)Figure 12: Summary of The Types of Studies That Have Been Used During Drug Development to Evaluate Therapeutic Protein (TP)–Small-Molecule Drug (D) Interactions. This includes an evaluation of the effect of TP on D (TP→D) and the effect of D on TP (D→TP). (PDF - 55KB)