Using a population mechanistic TMDD model calibrated on preclinical monkey data to simulate first-in-human
Keywords: monolix, PKPD modeling, Pre-Clinical, simulx, SLP2021MIDDSoftware: MonolixSuite™, Simulx™Conference: SLP MIDD+Division: Lixoft
Challenges for First-in-human
Which dose to choose to elicit the desired effect (efficacy), without causing harm (safety)?
No Observable Adverse Effect Level:
- Determine NOAEL dose in preclinical species
- Scale to human based on body-weight or BSA
- Add 10-fold safety margin
Minimal Anticipated Biological Effect Level:
- Requires to understand the PD (biological effect)
- PK/PD modeling can give valuable insight (e.g on receptor occupancy)
By Geraldine Ayral
Presented at SLP MIDD+ Virtual Conference March 3-4, 2021
