Tools and reference
Interactive tools, a glossary of pharmacometrics terms and catalogs that accompany the analyses by Daiki Kumakura, in Japanese and English.
About these analyses
How the analyses on this site are made, checked and corrected
Scope, sources, reproducibility, verification, limits and correction practice of the public-data analyses on this site, with how to report an error.
Tools
Pembrolizumab and nivolumab: exposure by body weight under fixed and weight-based dosing
Look up how often trough and peak exposure of pembrolizumab and nivolumab leave the trial-tested range at a given body weight under flat, weight-based and extended-interval regimens.
Glossary
PK fundamentals （PKの基礎）
PK accumulation ratio
An accumulation ratio compares the same exposure metric after repeated dosing and after the first dose.
薬物動態の蓄積比（日本語）
Apparent clearance and volume
After oral dosing, clearance and volume are commonly estimated relative to bioavailability as CL/F and V/F.
見かけのクリアランスと分布容積（日本語）
AUC (area under the concentration–time curve)
AUC is the area under the drug concentration–time curve over a period, a measure of total exposure. Divided by the length of a dosing interval it gives the average concentration.
AUC（濃度–時間曲線下面積）とは（日本語）
Bioavailability (F)
Bioavailability is the fraction of a dose that reaches the systemic circulation. With only oral data, F cannot be separated from clearance and volume; only CL/F and V/F can be estimated.
バイオアベイラビリティ（F）とは（日本語）
Clearance (CL)
Clearance is the volume of plasma from which a drug is completely removed per unit time. It sets the average concentration for a given dose rate and is the parameter most tied to exposure.
クリアランス（CL）とは（日本語）
Cmax (peak concentration)
Cmax is the highest drug concentration reached after a dose. At steady state it is written Cmax,ss. It matters for effects that depend on the peak, such as the first peak after a first dose.
Cmax（最高濃度）とは（日本語）
Ctrough (trough concentration)
Ctrough is the drug concentration measured just before the next dose, the lowest level within a dosing interval at steady state. It is used to compare dosing regimens, but a trough alone does not describe the whole exposure.
Ctrough（トラフ濃度）とは（日本語）
Dose proportionality
An exposure metric is dose proportional when it increases by the same factor as dose across a specified range.
用量比例性（日本語）
Dosing interval notation: Q2W, Q3W, Q4W and QD
Q2W means every 2 weeks, Q3W every 3 weeks and Q4W every 4 weeks; QD means once daily. The Q comes from the Latin quaque, "every".
Flip-flop kinetics
With slow absorption, the terminal slope after extravascular dosing can primarily reflect absorption.
フリップフロップ動態（日本語）
Half-life (t½)
The half-life is the time for a drug concentration to fall by half during elimination. It sets how long a drug takes to reach steady state and to wash out, and links clearance with volume of distribution.
半減期（t½）とは（日本語）
Noncompartmental analysis (NCA)
NCA calculates PK summaries from sampled concentrations and dosing records without specifying a compartmental structure.
ノンコンパートメント解析（NCA）（日本語）
One-compartment PK model
A one-compartment model treats the drug amount as a single well-mixed pool.
1コンパートメントPKモデル（日本語）
Same AUC with different dosing intervals
Equal exposure over the same time window can coexist with different peak and trough concentrations.
AUCが同じ場合の投与間隔と濃度推移（日本語）
Steady state in repeated dosing
At steady state the amount of drug entering the body per interval equals the amount leaving it, so the concentration profile repeats from dose to dose. Summary measures such as Ctrough,ss and Cavg,ss are taken at this point.
定常状態とは（繰り返し投与）（日本語）
Two-compartment PK model
This model exchanges drug between central and peripheral compartments.
2コンパートメントPKモデル（日本語）
Volume of distribution (V)
The volume of distribution relates the amount of drug in the body to its plasma concentration. In compartment models, V1 is the central volume and V2 the peripheral volume. It is a proportionality, not a physical volume.
分布容積（V）とは（日本語）
Population PK and model diagnostics （母集団PKとモデル診断）
Body weight as a covariate (allometric scaling)
A PK parameter is often scaled as typical value × (weight / reference weight)^exponent. Fitted exponents for antibodies are usually below one, which is why fixed and weight-based dosing give different exposure at the extremes.
Below the limit of quantification (BLQ)
A BLQ record indicates that a concentration falls below the assay's quantifiable range.
定量下限未満（BLQ）のPKデータ（日本語）
Eta shrinkage in PopPK
Individual random-effect estimates can cluster toward zero when the data carry little information about each patient.
母集団PKのη縮小（日本語）
Inter-individual variability (IIV)
Inter-individual variability is the spread of a PK parameter between patients, usually modeled as log-normal. Its variance ω² on the log scale corresponds to a coefficient of variation of about √(exp(ω²) − 1).
個体間変動（IIV）とは（日本語）
Interoccasion variability
Interoccasion variability represents changes in an individual PK parameter between prespecified occasions.
機会間変動（IOV）（日本語）
Reimplementing a published population PK model
Rebuilding a published population PK model from its tables and supplement in your own software, and checking that it reproduces the published values, lets you ask new questions without the original data.
公表された母集団PKモデルの再実装（日本語）
Population PK and nonlinear mixed-effects (NLME) models
A population PK model describes the typical concentration–time profile and how it varies between and within patients, estimated from the pooled, often sparse data of many patients with a nonlinear mixed-effects model.
Practical identifiability of PK/PD models
Practical identifiability asks whether real, noisy and finite data determine the parameters precisely enough. It depends on the sampling design, assay error and dose range, and shows up as bounded or flat likelihood profiles.
PK/PDモデルの実用的識別可能性（日本語）
Profile likelihood
A profile likelihood shows how the likelihood changes when one parameter is fixed at a range of values and the others are re-estimated. A bounded profile means the data determine the parameter; a flat one means they do not.
プロファイル尤度とは（日本語）
Residual variability in population PK
Residual variability describes the difference between a concentration measurement and its individual model prediction.
母集団PKの残差変動（日本語）
Sparse PK sampling
Population PK pools information across patients when each patient has only a few samples.
疎なPK採血（日本語）
Structural identifiability of PK/PD models
Structural identifiability asks whether the parameters of a model can be determined uniquely from ideal, noise-free data of the chosen outputs. It depends on the model and the design, not on the data collected.
PK/PDモデルの構造的識別可能性（日本語）
Visual predictive check (VPC)
A VPC compares observed summaries with their distribution under repeated simulation of the study design.
PK/PD and exposure–response （PK/PDと曝露–反応）
C-index (concordance index)
The C-index is the probability that, for two comparable patients, the one with the higher predicted risk has the shorter survival. 0.5 is chance and 1 is perfect ordering. A gain in C-index is not by itself clinical usefulness.
C-index（一致指数）とは（日本語）
Concentration–QTc analysis
A concentration–QTc analysis assesses the association between exposure and heart-rate-corrected QT interval.
濃度–QTc解析（日本語）
Cytokine release syndrome (CRS)
Cytokine release syndrome is a systemic inflammatory reaction after strong immune-cell activation, for example by T-cell engaging antibodies or CAR-T cells. It is graded by severity and is the reason for step-up dosing.
サイトカイン放出症候群（CRS）とは（日本語）
Dose intensity
Dose intensity is the amount of drug given per unit time, for example mg per week. Changing the interval while keeping dose intensity constant preserves the average concentration but changes the peak and the trough.
Effect compartment models
An effect compartment represents a delay between plasma concentration and the concentration driving response.
効果コンパートメントモデル（日本語）
Emax and Hill models (EC50)
The Emax model describes an effect that rises with concentration to a maximum. EC50 is the concentration giving half of the maximum effect, and the Hill exponent sets the steepness.
Choosing an exposure metric
The exposure metric and time window should match the biological question and outcome timing.
曝露指標の選び方（日本語）
Exposure–response analysis
Exposure–response analysis relates an exposure measure such as AUC or Ctrough to an efficacy or safety endpoint. It is used to justify a dose, but confounding can make the relationship look steeper than it is.
Confounding in exposure–response analysis
An exposure–response association can reflect factors that influence both exposure and the clinical outcome.
曝露–反応解析における交絡（日本語）
Fixed (flat) dosing versus weight-based dosing
Fixed dosing gives every patient the same dose; weight-based dosing scales it by body weight (mg/kg). For antibodies the difference matters mainly at the ends of the weight distribution.
固定用量と体重換算用量（日本語）
Indirect response (turnover) models
An indirect response model describes an effect that arises when a drug changes the production or loss of a response variable that turns over in the body, so the effect lags behind the plasma concentration.
間接反応（ターンオーバー）モデルとは（日本語）
Landmark analysis
A landmark analysis fixes a time point, uses only information available by then as predictors, and studies the outcome after it. It avoids using the future to predict the future.
ランドマーク解析（日本語）
PK/PD models
A PK/PD model connects the concentration over time to a pharmacological response.
PK/PDモデル（日本語）
Project Optimus and dose optimization in oncology
Project Optimus is an initiative of the US FDA Oncology Center of Excellence to improve dose selection in oncology drug development, moving beyond the maximum tolerated dose to doses with the best benefit–risk, supported by randomized dose comparisons.
Receptor occupancy (RO)
Receptor occupancy is the fraction of target receptors bound by a drug. For simple binding it follows RO = C / (C + Kd), and it is a step between drug concentration and pharmacological effect.
受容体占有率（RO）とは（日本語）
Step-up dosing of T-cell engaging bispecific antibodies
Step-up dosing starts with a small dose and increases it over the first cycle to the target dose, to lower the first concentration peak. A lower peak does not by itself tell how much cytokine release syndrome is reduced.
PBPK and drug interactions （PBPKと薬物相互作用）
Pharmacokinetic drug interactions (DDI)
A drug interaction can alter exposure through changes in enzymes, transporters or absorption.
薬物動態学的な薬物相互作用（DDI）（日本語）
Food effect on drug exposure
Food can change the rate or extent of absorption after oral administration.
食事による薬物曝露の変化（日本語）
Fraction metabolized (fm)
The fraction metabolized describes how much of overall elimination is attributable to a specified metabolic pathway under defined conditions.
代謝寄与率（fm）（日本語）
Physiologically based pharmacokinetics (PBPK)
PBPK represents drug movement through tissues using physiology and drug-specific properties.
生理学的薬物動態モデル（PBPK）（日本語）
PBPK vs population PK
PBPK describes physiology and drug movement. Population PK estimates typical kinetics and variability from pooled observations.
PBPKと母集団PKの違い（日本語）
Unbound drug concentration
Unbound concentration is the fraction of total drug concentration that is free of binding in the sampled matrix.
非結合型薬物濃度（日本語）
Toxicokinetics and safety （毒性動態と安全性）
Exposure margins in toxicology
An exposure margin compares exposure at a defined nonclinical dose with exposure under a specified human regimen.
毒性評価における曝露マージン（日本語）
No observed adverse effect level (NOAEL)
The NOAEL is the highest tested dose without an observed adverse effect under the study conditions.
無毒性量（NOAEL）（日本語）
Quantitative systems toxicology (QST)
QST links exposure and mechanisms of biological injury in a quantitative model.
定量的システム毒性学（QST）（日本語）
Toxicokinetics (TK)
Toxicokinetics measures systemic exposure in toxicity studies and relates it to dose, duration and observed findings.
毒性動態（トキシコキネティクス）（日本語）
QSP and model-informed development （QSPとモデルに基づく開発）
Model-informed drug development (MIDD)
MIDD integrates data and quantitative models to inform a defined drug development decision.
モデルに基づく医薬品開発（MIDD）（日本語）
Pharmacometrics
Uses quantitative models of drug exposure, response and variability to support drug development decisions.
Question of interest (QOI) and context of use (COU)
QOI is the specific question a modeling analysis answers; COU is how the result will be used. Stating both before the analysis keeps the claim within what the data support.
QOI（問い）とCOU（使いみち）（日本語）
Quantitative systems pharmacology (QSP)
QSP models connect drug action to interacting biological processes and their dynamics.
定量的システム薬理学（QSP）（日本語）
QSP model verification and validation
Verification checks the implementation. Validation assesses whether model predictions reproduce relevant observations for the intended use.
QSPモデルの検証と妥当性評価（日本語）
Robust mixture prior and borrowing from an existing drug
A robust mixture prior combines an informative component from existing data with a vague component, weighted by a borrowing weight. It is meant to reduce borrowing when new data conflict, but with small samples it may hardly do so.
頑健な混合事前分布と、既存薬の情報の借用（日本語）
T-cell engaging bispecific antibodies (T-cell engagers)
A T-cell engager is a bispecific antibody that binds a tumor-surface antigen on one arm and CD3 on T cells on the other, bringing T cells to the tumor cell. Examples are mosunetuzumab (CD20) and tarlatamab (DLL3).
Target-mediated drug disposition (TMDD)
In target-mediated drug disposition, binding to the pharmacological target contributes to the drug’s distribution and elimination. Because the target can saturate, clearance falls at higher concentrations and PK is nonlinear.
標的介在性薬物動態（TMDD）とは（日本語）
Tumor growth inhibition (TGI) models
TGI models describe longitudinal tumor measurements and the effects of treatment on growth or shrinkage.
腫瘍増殖抑制（TGI）モデル（日本語）
Virtual patients and virtual populations
Virtual patients are sets of model inputs used to simulate plausible individual trajectories under specified scenarios.
仮想患者と仮想集団（日本語）
Catalogs
Published PK and PK/PD models used in the analyses
A catalog of the published population PK and PK/PD models reimplemented, fitted or reused in the analyses on this site, with source papers, structure, what was done and the article.