Understanding the dose-effect relationship¶
Holford, N. H. G., & Sheiner, L. B. (1981). Understanding the dose-effect relationship: Clinical application of pharmacokinetic-pharmacodynamic models. Clinical Pharmacokinetics, 6(6), 429-453.
Cited by¶
2 citations across 2 artifacts.
Each citation links to the sentence it supports in the citing article.
Primes¶
- Dose-Response Relationship
- It licenses formal modeling in pharmacokinetic-pharmacodynamic frameworks, supports design of dose-finding trials, and underlies regulatory risk assessment, an integrative approach Holford and Sheiner (1981) articulated when they argued that the dose-effect relationship can be properly understood only by linking PK (concentration over time) to PD (effect as a function of concentration) through explicit Hill-equation-style models.
This sourceFoundational PK/PD synthesis arguing the dose-effect relationship requires linking PK (concentration over time) to PD (effect vs concentration) via Hill-equation models; supports D47-028 (formal reasoning across the full dose-response framework).
Supported in partVerified against the publisher's abstract
Abstract supports linking PK to PD for the dose-effect relationship, but not dose-finding trials, regulatory risk assessment, or a Hill equation.
“However, the time course of drug concentration cannot in itself predict the time course or magnitude of drug effect.”
- It licenses formal modeling in pharmacokinetic-pharmacodynamic frameworks, supports design of dose-finding trials, and underlies regulatory risk assessment, an integrative approach Holford and Sheiner (1981) articulated when they argued that the dose-effect relationship can be properly understood only by linking PK (concentration over time) to PD (effect as a function of concentration) through explicit Hill-equation-style models.
- PK/PD Modeling (Pharmacokinetics / Pharmacodynamics)
- T3: PK/PD Disconnect Between Plasma and Effect Site. For drugs with slow distribution to the effect site (CNS drugs crossing the blood-brain barrier; tissue-localized antibiotics; intracellular targets), plasma concentration and effect-site concentration dissociate, producing hysteresis — effect lags behind concentration or persists after concentration has fallen — the canonical effect-compartment phenomenon Holford and Sheiner (1981) formalized for time-resolved exposure-response analysis.
This sourceFoundational PK/PD synthesis: argues that the dose-effect relationship requires linking pharmacokinetics (concentration over time) to pharmacodynamics (effect as a function of concentration) through Hill-equation models, formalizing reasoning across the full dose-response framework.
Supported in partVerified against the publisher's abstract
Abstract backs the PK/PD link between concentration and effect, but never states hysteresis, a lag, or an effect-compartment model.
“However, the time course of drug concentration cannot in itself predict the time course or magnitude of drug effect.”
- T3: PK/PD Disconnect Between Plasma and Effect Site. For drugs with slow distribution to the effect site (CNS drugs crossing the blood-brain barrier; tissue-localized antibiotics; intracellular targets), plasma concentration and effect-site concentration dissociate, producing hysteresis — effect lags behind concentration or persists after concentration has fallen — the canonical effect-compartment phenomenon Holford and Sheiner (1981) formalized for time-resolved exposure-response analysis.
Verification¶
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