Population Pharmacokinetics in Drug Development

1 List of Acronyms

• CL_tot total clearancepopulation pharmacokinetic

• CL_CR creatinine clearance

• CONC observed concentration

• C_ss concentration at steady-state

• η random inter-individual variability η∼N(0, ω²)

• HT height in cm

• IPRE model predictions for the individual subject with random η_i

• LBM lean body mass in kg

• MIC minimum inhibitory concentration

• NAD naive averaging data method

• NONMEM nonlinear mixed-effects modeling

• NPD naive pooled data

• OF objective function: negative log of probability, − 2ln(Prob), OFV calculated by NONMEM

• ω² covariance matrix describing the between subject variability η_i ∼ N(0, ω²)

• PK pharmacokinetics

• PPK population pharmacokinetic

• PRED model predictions for the population with η = 0

• SEX 1 = male and 2 = female

• σ² covariance matrix describing the within subject or residual variability ε_i ∼ N(0, σ²)

• STS standard two stage method

• θ Vector of parameter, describing the fixed effect model

• V volume of distribution

• WT body weight [kg]

2 Purpose and Rationale

Variability...