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Pharmacodynamic principles and the time course of immediate drug effects
Nick Holford 대한임상약리학회 2017 Translational and Clinical Pharmacology Vol.25 No.4
This tutorial defines the principles of the concentration . effect relationship which are the basis ofpharmacodynamics. The two key parameters of pharmacodynamics are the maximum response(Emax) and the concentration producing 50% of Emax (C50). The time course of effect is illustratedunder the assumption that drug effects are immediately related to concentration in the centralcompartment e.g. plasma. The related idea of duration of drug action and its relationship to dose isshown to have a simple relationship with drug half-life.
Pharmacokinetic variability due to environmental differences
Nick Holford 대한임상약리학회 2017 Translational and Clinical Pharmacology Vol.25 No.2
This tutorial describes sources of pharmacokinetic variability that are not obviously linked to geneticdifferences. The sources of variability are therefore described as environmental. The majorquantitative sources of environmental variability are body size (including body composition), maturationand organ function. Size should be considered in all patients. Maturation is mainly relevantto neonates and infants less than 2 years of age. Renal function is the most important predictablesource of variability due to differences in organ function.
Pharmacodynamic principles and the time course of delayed and cumulative drug effects
Nick Holford 대한임상약리학회 2018 Translational and Clinical Pharmacology Vol.26 No.2
This tutorial reviews the principles of the concentration . effect relationship for the usual casewhen drug effects are delayed relative to changes in circulating concentrations. The key processesdetermining delay are distribution from the circulation to the receptor, binding to the receptorto produce a stimulus and translation of the receptor stimulus into an effect through turnover ofphysiological mediators. Some clinical outcomes are dependent on the accumulation of drug actionwhich is predictable in terms of basic pharmacokinetic and pharmacodynamic concepts.
Treatment response and disease progression
Nick Holford 대한임상약리학회 2019 Translational and Clinical Pharmacology Vol.27 No.4
This tutorial defines the concepts of disease progression in the context of clinical pharmacology. Disease progression describes the natural history of disease, such as pain, or biomarker of drugresponse, such as blood pressure. The action of a drug, such as inhibiting an enzyme or activating areceptor, leads to a change in disease status over time. Two main types of drug response can be definedbased on the pattern of the time course of disease status. The most common is a symptomaticeffect equivalent to a shift up or down of the natural history curve. Less common but quite clinicallyimportant is a disease-modifying effect equivalent to a change in the rate of disease progression.
Pharmacodynamic principles and target concentration intervention
Nick Holford 대한임상약리학회 2018 Translational and Clinical Pharmacology Vol.26 No.4
This tutorial reviews the principles of dose individualisation with an emphasis on target concentrationintervention (TCI). Once a target effect is chosen then pharmacodynamics can predictthe target concentration and pharmacokinetics can predict the target dose to achieve the requiredresponse. Dose individualisation can be considered at three levels: population, group and individual. Population dosing, also known as fixed dosing or “one size fits all” is often used but is poorclinical pharmacology; group dosing uses patient features such as weight, organ function and comedicationto adjust the dose for a typical patient; individual dosing uses observations of patientresponse to inform about pharmacokinetic and pharmacodynamics in the individual and use theseindividual differences to individualise dose.
Nick Holford 대한임상약리학회 2016 Translational and Clinical Pharmacology Vol.24 No.4
This tutorial deals with basic concepts of absorption processes and links previous tutorials on clearance and volume of distribution to introduce the concept of half-life. The time course of both absorption and elimination are commonly described using a half-life. Half-life can also be used to describe drug accumulation. Understanding the principles underlying the time course of absorp¬tion and elimination are essential in pharmacotherapy and clinical pharmacology.
Nick Holford,임동석 대한임상약리학회 2015 Translational and Clinical Pharmacology Vol.23 No.2
This tutorial deals with basic concepts of clearance, the most important parameter in pharmacokineticsbut often challenging for students in clinical pharmacology. Its relationships with dose, concentrationand elimination rate are discussed using a physical model and examples of commonlyused drugs, as well as its physiological aspects pertaining to the blood flow to differing organs. Finally, application of clearance to the calculation of maintenance dose rate and half-life is used toshow how it is essential in pharmacotherapy and clinical pharmacology
Nick Holford,임동석 대한임상약리학회 2016 Translational and Clinical Pharmacology Vol.24 No.2
This tutorial deals with basic concepts of volume of distribution, the second most important param¬eter in pharmacokinetics but often challenging for students in clinical pharmacology. Its relation¬ships with dose, concentration and amount in the body are discussed using a physical model and examples of commonly used drugs, as well as its physiological aspects pertaining to the physical vol¬ume of differing organs. Finally, application of volume of distribution to the calculation of loading dose and half-life is used to show how it is essential in pharmacotherapy and clinical pharmacology.