Pharmacokinetics

Pharmacokinetics (from Ancient Greek pharmakon "drug" and kinetikos "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific substance after administration.^[1] The substances of interest include any chemical xenobiotic such as pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is based on mathematical modeling that places great emphasis on the relationship between drug plasma concentration and the time elapsed since the drug's administration. Pharmacokinetics is the study of how an organism affects the drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models.

IUPAC definition

Pharmacokinetics:

Process of the uptake of drugs by the body, the biotransformation they undergo, the distribution of the drugs and their metabolites in the tissues, and the elimination of the drugs and their metabolites from the body over a period of time.

Study of more such related processes^[2]

ADME

A number of phases occur once the drug enters into contact with the organism, these are described using the acronym ADME (or LADME if liberation is included as a separate step from absorption):

Liberation – the process of the active ingredient separating from its pharmaceutical formulation.^[3]^[4] See also IVIVC.
Absorption – the process of a drug entering into systemic circulation from the site of administration
Distribution – the dispersion or dissemination of substances throughout the fluids and tissues of the body.
Metabolism (or biotransformation, or inactivation) – the chemical reactions of the drug and irreversible breakdown into metabolites (e.g. by metabolic enzymes such as cytochrome P450 or glucuronosyltransferase enzymes)
Excretion – the removal of the substance or metabolites from the body. In rare cases, some drugs irreversibly accumulate in body tissue. ^{[citation needed]}

Some textbooks combine the first two phases as the drug is often administered in an active form, which means that there is no liberation phase. Others include a phase that combines distribution, metabolism and excretion into a disposition phase. Other authors include the drug's toxicological aspect in what is known as ADME-Tox or ADMET. The two phases of metabolism and excretion can be grouped together under the title elimination.

The study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. For this reason, in order to fully comprehend the kinetics of a drug it is necessary to have detailed knowledge of a number of factors such as: the properties of the substances that act as excipients, the characteristics of the appropriate biological membranes and the way that substances can cross them, or the characteristics of the enzyme reactions that inactivate the drug.

Metrics

The following are the most commonly measured pharmacokinetic metrics:^[5] The units of the dose in the table are expressed in moles (mol) and molar (M). To express the metrics of the table in units of mass, instead of Amount of substance, simply replace 'mol' with 'g' and 'M' with 'g/dm3'. Similarly, other units in the table may be expressed in units of an equivalent dimension by scaling.^[6]

Pharmacokinetic metrics
Characteristic	Description	Symbol	Unit	Formula	Worked example value
Dose	Amount of drug administered.	$D$	$\mathrm {mol}$	Design parameter	500 mmol
Dosing interval	Time interval between drug dose administrations.	$\tau$	$\mathrm {h}$	Design parameter	24 h
Maximum serum concentration	The peak plasma concentration of a drug after administration.	$C_{\text{max}}$	$\mathrm {mmol/L}$	Direct measurement	60.9 mmol/L
Minimum time for Cmax	Minimum time taken to reach C_max.	$t_{\text{max}}$	$\mathrm {h}$	Direct measurement	3.9 h
Minimum plasma concentration	The lowest (trough) concentration that a drug reaches before the next dose is administered.	$C_{{\text{min}},{\text{ss}}}$	$\mathrm {mmol/L}$	$C_{min}={\frac {SFDk_{a}}{V_{d}(k_{a}-k)}}\times \{{\frac {e^{-k_{e}\tau }}{1-e^{-k_{e}\tau }}}-{\frac {e^{-k_{a}\tau }}{1-e^{-k_{a}\tau }}}\}$	27.7 mmol/L
Average plasma concentration	The average plasma concentration of a drug over the dosing interval in steady state.	$C_{{\text{av}},{\text{ss}}}$	$\mathrm {h\times mmol/L}$	${\frac {AUC_{\tau ,{\text{ss}}}}{\tau }}$	55.0 h×mmol/L
Volume of distribution	The apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration in plasma to drug amount in the body).	$V_{\text{d}}$	$\mathrm {L}$	${\frac {D}{C_{0}}}$	6.0 L
Concentration	Amount of drug in a given volume of plasma.	$C_{0},C_{\text{ss}}$	$\mathrm {mmol/L}$	${\frac {D}{V_{\text{d}}}}$	83.3 mmol/L
Absorption half-life	The time required for 50% of a given dose of drug to be absorbed into the systemic circulation.^[7]	$t_{{\frac {1}{2}}a}$	$\mathrm {h}$	${\frac {\ln(2)}{k_{\text{a}}}}$	1.0 h
Absorption rate constant	The rate at which a drug enters into the body for oral and other extravascular routes.	$k_{\text{a}}$	$\mathrm {h} ^{-1}$	${\frac {\ln(2)}{t_{{\frac {1}{2}}a}}}$

[1]

[2]

[3]

[4]

[5]

[6]

[7]