Pharmacokinetics
From Wikipedia, the free encyclopedia
Graph that demonstrates the Michaelis-Menten kinetics model for the relationship between an enzyme and a substrate: one of the parameters studies in pharmacokinetics, where the substrate is a pharmaceutical drug.
Pharmacokinetics, sometimes abbreviated as PK (from Ancient Greek pharmakon "drug" and kinetikos "moving, putting in motion"; see chemical kinetics), is a branch of pharmacology dedicated to determining the fate of substances administered externally to a living organism. The substances of interest include pharmaceutical agents, hormones, nutrients, and toxins. It attempts to discover the fate of a drug from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics describes how the body affects a specific drug after administration through the mechanisms of absorption and distribution, as well as the chemical changes of the substance in the body (e.g. by metabolic enzymes such as cytochrome P450 or glucuronosyltransferase enzymes), and the effects and routes of excretion of the metabolites of the drug. Pharmacokinetic properties of drugs may be affected by elements such as the site of administration and the dose of administered drug. These may affect the absorption rate. Pharmacokinetics is often studied in conjunction with pharmacodynamics, the study of a drug's pharmacological effect on the body.
A number of different models have been developed in order to simplify conceptualization of the many processes that take place in the interaction between an organism and a drug. One of these models, the multi-compartment model, gives the best approximation to reality; however, the complexity involved in using this type of model means that monocompartmental models and above all two compartmental models are the most-frequently used. The various compartments that the model is divided into is commonly referred to as the ADME scheme (also referred to as LADME if liberation is included as a separate step from absorption):
All these concepts can be represented through mathematical formulas that have a corresponding graphical representation. The use of these models allows an understanding of the characteristics of a molecule, as well as how a particular drug will behave given information regarding some of its basic characteristics. Such as its acid dissociation constant (pKa), bioavailability and solubility, absorption capacity and distribution in the organism.
The model outputs for a drug can be used in industry (for example, in calculating bioequivalence when designing generic drugs) or in the clinical application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in veterinary medicine.
Contents
Metrics
The following are the most commonly measured pharmacokinetic metrics:
CharacteristicDescriptionExample valueSymbolFormulaDoseAmount of drug administered.500 mgDesign parameterDosing intervalTime between drug dose administrations.24 hDesign parameterCmaxThe peak plasma concentration of a drug after administration.60.9 mg/LDirect measurementtmaxTime to reach Cmax.3.9 hDirect measurementCminThe lowest (trough) concentration that a drug reaches before the next dose is administered.27.7 mg/LDirect measurementVolume of distributionThe apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration to drug amount in the body).6.0 LConcentrationAmount of drug in a given volume of plasma.83.3 mg/LElimination half-lifeThe time required for the concentration of the drug to reach half of its original value.12 hElimination rate constantThe rate at which a drug is removed from the body.0.0578 h−1Infusion rateRate of infusion required to balance elimination.50 mg/hArea under the curveThe integral of the concentration-time curve (after a single dose or in steady state).1,320 mg/L·hClearanceThe volume of plasma cleared of the drug per unit time.0.38 L/hBioavailabilityThe systemically available fraction of a drug.0.8FluctuationPeak trough fluctuation within one dosing interval at steady state41.8 %
In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination. In practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started.
From Wikipedia, the free encyclopedia
Graph that demonstrates the Michaelis-Menten kinetics model for the relationship between an enzyme and a substrate: one of the parameters studies in pharmacokinetics, where the substrate is a pharmaceutical drug.
Pharmacokinetics, sometimes abbreviated as PK (from Ancient Greek pharmakon "drug" and kinetikos "moving, putting in motion"; see chemical kinetics), is a branch of pharmacology dedicated to determining the fate of substances administered externally to a living organism. The substances of interest include pharmaceutical agents, hormones, nutrients, and toxins. It attempts to discover the fate of a drug from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics describes how the body affects a specific drug after administration through the mechanisms of absorption and distribution, as well as the chemical changes of the substance in the body (e.g. by metabolic enzymes such as cytochrome P450 or glucuronosyltransferase enzymes), and the effects and routes of excretion of the metabolites of the drug. Pharmacokinetic properties of drugs may be affected by elements such as the site of administration and the dose of administered drug. These may affect the absorption rate. Pharmacokinetics is often studied in conjunction with pharmacodynamics, the study of a drug's pharmacological effect on the body.
A number of different models have been developed in order to simplify conceptualization of the many processes that take place in the interaction between an organism and a drug. One of these models, the multi-compartment model, gives the best approximation to reality; however, the complexity involved in using this type of model means that monocompartmental models and above all two compartmental models are the most-frequently used. The various compartments that the model is divided into is commonly referred to as the ADME scheme (also referred to as LADME if liberation is included as a separate step from absorption):
- Liberation - the process of release of a drug from the pharmaceutical formulation. See also IVIVC.
- Absorption - the process of a substance entering the blood circulation.
- Distribution - the dispersion or dissemination of substances throughout the fluids and tissues of the body.
- Metabolization (or biotransformation, or inactivation) – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites.
- Excretion - the removal of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue.
All these concepts can be represented through mathematical formulas that have a corresponding graphical representation. The use of these models allows an understanding of the characteristics of a molecule, as well as how a particular drug will behave given information regarding some of its basic characteristics. Such as its acid dissociation constant (pKa), bioavailability and solubility, absorption capacity and distribution in the organism.
The model outputs for a drug can be used in industry (for example, in calculating bioequivalence when designing generic drugs) or in the clinical application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in veterinary medicine.
Contents
- 1 Metrics
- 2 Pharmacokinetic models
- 3 Bioavailability
- 4 LADME
- 5 Analysis
- 6 Population pharmacokinetics
- 7 Clinical pharmacokinetics
- 8 Ecotoxicology
- 9 Software
- 10 Educational centres
- 11 See also
- 12 References
- 13 External links
Metrics
The following are the most commonly measured pharmacokinetic metrics:
CharacteristicDescriptionExample valueSymbolFormulaDoseAmount of drug administered.500 mgDesign parameterDosing intervalTime between drug dose administrations.24 hDesign parameterCmaxThe peak plasma concentration of a drug after administration.60.9 mg/LDirect measurementtmaxTime to reach Cmax.3.9 hDirect measurementCminThe lowest (trough) concentration that a drug reaches before the next dose is administered.27.7 mg/LDirect measurementVolume of distributionThe apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration to drug amount in the body).6.0 LConcentrationAmount of drug in a given volume of plasma.83.3 mg/LElimination half-lifeThe time required for the concentration of the drug to reach half of its original value.12 hElimination rate constantThe rate at which a drug is removed from the body.0.0578 h−1Infusion rateRate of infusion required to balance elimination.50 mg/hArea under the curveThe integral of the concentration-time curve (after a single dose or in steady state).1,320 mg/L·hClearanceThe volume of plasma cleared of the drug per unit time.0.38 L/hBioavailabilityThe systemically available fraction of a drug.0.8FluctuationPeak trough fluctuation within one dosing interval at steady state41.8 %
In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination. In practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started.