Glossary¶
Common pharmacometrics and NeoPKPD terminology.
A¶
Absorption Rate Constant (Ka) : First-order rate constant describing the rate of drug absorption from the gut to systemic circulation. Units: 1/h.
AUC (Area Under the Curve) : Total drug exposure over time, calculated as the integral of concentration over time. Units: mg·h/L.
AUC0-t : Area under the concentration-time curve from time zero to the last measurable concentration.
AUC0-inf : Area under the concentration-time curve extrapolated to infinity.
B¶
Bioavailability (F) : Fraction of administered dose that reaches systemic circulation unchanged. Range: 0-1.
Bioequivalence (BE) : Demonstration that two formulations have similar bioavailability within defined limits (typically 80-125% for the 90% CI of the geometric mean ratio).
BLQ (Below Limit of Quantification) : Concentration measurement below the lower limit of quantification of the analytical assay.
C¶
Clearance (CL) : Volume of plasma from which drug is completely removed per unit time. Units: L/h.
Cmax : Maximum observed concentration. Units: mg/L.
Compartment : Theoretical space in which drug is assumed to distribute uniformly and instantaneously.
CWRES (Conditional Weighted Residuals) : Residuals weighted by the conditional variance, used for model diagnostics.
D¶
Distribution : Process by which drug reversibly transfers between blood and tissues.
Dose Event : A single drug administration with time, amount, and optional duration (for infusions).
E¶
EBE (Empirical Bayes Estimate) : Individual parameter estimates derived using Bayesian estimation with population parameters as priors.
EC50 : Concentration producing 50% of maximum effect. Units: mg/L.
Effect Compartment : Hypothetical compartment representing the site of drug action, used to model PK-PD delays.
Emax : Maximum achievable drug effect.
Eta (η) : Random effect representing individual deviation from the typical population parameter value.
F¶
FOCE (First-Order Conditional Estimation) : NLME estimation method that linearizes the model around individual parameter estimates.
FOCE-I (FOCE with Interaction) : FOCE method that accounts for the interaction between random effects and residual error.
G¶
Gamma (γ) : Hill coefficient in the sigmoid Emax model, controlling the steepness of the concentration-response curve.
H¶
Half-life (t½) : Time required for drug concentration to decrease by 50%. Calculated as ln(2)/λz.
Hill Coefficient : See Gamma.
I¶
IIV (Inter-Individual Variability) : Random variability in pharmacokinetic or pharmacodynamic parameters between subjects in a population.
Indirect Response Model : PD model where drug affects the rate of production or elimination of a response variable rather than the response directly.
IOV (Inter-Occasion Variability) : Random variability in parameters within the same subject across different occasions.
K¶
Km (Michaelis Constant) : Concentration at which the elimination rate is half of Vmax in saturable kinetics. Units: mg/L.
L¶
Lambda_z (λz) : Terminal elimination rate constant, estimated from the terminal log-linear phase of the concentration-time curve. Units: 1/h.
LLOQ (Lower Limit of Quantification) : Lowest concentration that can be reliably measured with acceptable precision and accuracy.
M¶
MRT (Mean Residence Time) : Average time a drug molecule spends in the body. Calculated as AUMC/AUC.
Michaelis-Menten : Nonlinear elimination kinetics characterized by Vmax and Km, where elimination rate saturates at high concentrations.
N¶
NCA (Non-Compartmental Analysis) : Model-independent method for calculating PK parameters directly from concentration-time data.
NLME (Nonlinear Mixed Effects) : Statistical framework for analyzing population data with both fixed and random effects.
NPDE (Normalized Prediction Distribution Errors) : Diagnostic metric based on the cumulative distribution of observations relative to simulations.
O¶
OFV (Objective Function Value) : Negative twice the log-likelihood; minimized during parameter estimation. Lower is better for nested models.
Omega (Ω) : Variance-covariance matrix of inter-individual random effects.
P¶
pcVPC (Prediction-Corrected VPC) : VPC variant that corrects predictions for differences in independent variables across bins.
Population PK : Approach to characterize typical PK parameters and their variability in a population.
Q¶
Q (Inter-compartmental Clearance) : Rate of drug transfer between compartments. Units: L/h.
R¶
Residual Error : Unexplained variability between model predictions and observations, including measurement error and model misspecification.
RSE (Relative Standard Error) : Standard error expressed as a percentage of the parameter estimate.
S¶
SAEM (Stochastic Approximation EM) : NLME estimation algorithm using stochastic approximation for robust parameter estimation.
Shrinkage : Phenomenon where individual parameter estimates are pulled toward population values due to limited individual data.
Sigma (σ) : Variance of residual error.
T¶
Theta (θ) : Fixed-effect (typical population) parameter values.
Tmax : Time at which Cmax occurs. Units: h.
TMDD (Target-Mediated Drug Disposition) : PK behavior where drug binding to target significantly affects its disposition.
Transit Compartment : Series of compartments used to model delayed or complex absorption processes.
V¶
Vmax : Maximum rate of saturable elimination. Units: mg/h.
Volume of Distribution (V) : Apparent volume into which drug distributes at steady state. Units: L.
VPC (Visual Predictive Check) : Graphical method for assessing model adequacy by comparing observed data percentiles to simulated prediction intervals.
Vss (Volume of Distribution at Steady State) : Volume relating amount of drug in body to plasma concentration at steady state.
W¶
Washout Period : Time between treatment periods in crossover studies to allow drug elimination before the next period.
Abbreviations¶
| Abbreviation | Full Term |
|---|---|
| AUC | Area Under the Curve |
| BE | Bioequivalence |
| BID | Twice Daily |
| BLQ | Below Limit of Quantification |
| CDISC | Clinical Data Interchange Standards Consortium |
| CI | Confidence Interval |
| CL | Clearance |
| CV | Coefficient of Variation |
| EBE | Empirical Bayes Estimate |
| FDA | Food and Drug Administration |
| FOCE | First-Order Conditional Estimation |
| GOF | Goodness of Fit |
| IIV | Inter-Individual Variability |
| IOV | Inter-Occasion Variability |
| IV | Intravenous |
| NCA | Non-Compartmental Analysis |
| NLME | Nonlinear Mixed Effects |
| NPDE | Normalized Prediction Distribution Error |
| ODE | Ordinary Differential Equation |
| OFV | Objective Function Value |
| PD | Pharmacodynamics |
| PK | Pharmacokinetics |
| QD | Once Daily |
| RSE | Relative Standard Error |
| SAEM | Stochastic Approximation EM |
| SDTM | Study Data Tabulation Model |
| SE | Standard Error |
| TID | Three Times Daily |
| TMDD | Target-Mediated Drug Disposition |
| TOST | Two One-Sided Tests |
| VPC | Visual Predictive Check |