Pharmacokinetics

(Redirected from Pharmacokinetic)
Jump to: navigation, search

WikiDoc Resources for

Pharmacokinetics

Articles

Most recent articles on Pharmacokinetics

Most cited articles on Pharmacokinetics

Review articles on Pharmacokinetics

Articles on Pharmacokinetics in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Pharmacokinetics

Images of Pharmacokinetics

Photos of Pharmacokinetics

Podcasts & MP3s on Pharmacokinetics

Videos on Pharmacokinetics

Evidence Based Medicine

Cochrane Collaboration on Pharmacokinetics

Bandolier on Pharmacokinetics

TRIP on Pharmacokinetics

Clinical Trials

Ongoing Trials on Pharmacokinetics at Clinical Trials.gov

Trial results on Pharmacokinetics

Clinical Trials on Pharmacokinetics at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Pharmacokinetics

NICE Guidance on Pharmacokinetics

NHS PRODIGY Guidance

FDA on Pharmacokinetics

CDC on Pharmacokinetics

Books

Books on Pharmacokinetics

News

Pharmacokinetics in the news

Be alerted to news on Pharmacokinetics

News trends on Pharmacokinetics

Commentary

Blogs on Pharmacokinetics

Definitions

Definitions of Pharmacokinetics

Patient Resources / Community

Patient resources on Pharmacokinetics

Discussion groups on Pharmacokinetics

Patient Handouts on Pharmacokinetics

Directions to Hospitals Treating Pharmacokinetics

Risk calculators and risk factors for Pharmacokinetics

Healthcare Provider Resources

Symptoms of Pharmacokinetics

Causes & Risk Factors for Pharmacokinetics

Diagnostic studies for Pharmacokinetics

Treatment of Pharmacokinetics

Continuing Medical Education (CME)

CME Programs on Pharmacokinetics

International

Pharmacokinetics en Espanol

Pharmacokinetics en Francais

Business

Pharmacokinetics in the Marketplace

Patents on Pharmacokinetics

Experimental / Informatics

List of terms related to Pharmacokinetics

Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

Pharmacokinetics (in Greek: "pharmacon" meaning drug and "kinetikos" meaning putting in motion, the study of time dependency) is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. In practice, this discipline is applied mainly to drug substances, though in principle it concerns itself with all manner of compounds ingested or otherwise delivered externally to an organism, such as nutrients, metabolites, hormones, toxins, etc. Pharmacokinetics is often divided into several areas including, but not limited to, the extent and rate of Absorption, Distribution, Metabolism and Excretion. This sometimes is referred to as the ADME scheme.

Absorption is the process of a substance entering the body. Distribution is the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism is the irreversible transformation of substances and its daughter metabolites. Excretion is the elimination of the substances from the body. In rare cases, some drugs irreversibly accumulate in a tissue in the body.

Pharmacokinetics is often studied in conjunction with pharmacodynamics. So while pharmacodynamics explores what a drug does to the body, pharmacokinetics explores what the body does to the drug.

Pharmacokinetics is sometimes abbreviated as "PK".

Drug properties that influnce its pharmacokinetics

Partition coefficient

The partition or distribution coefficient (KD) is the ratio of concentrations of a compound in the two phases of a mixture of two immiscible solvents at equilibrium.[1]. It can influence the ADME properties (Absorption, Distribution, Metabolism, and Excretion) of the drug. When orally administered drugs are absorbed they must first pass through lipid bilayers in the intestinal epithelium (a process known as transcellular transport). For efficient transport, the drug must be hydrophobic enough to partition into the lipid bilayer, but not so hydrophobic, that once it is in the bilayer, it will not partition out again.[2]. The partition coefficient is dependent on the hydrophobic or hydrophilic properties of the drug.

Pharmacokinetic Analysis

Pharmacokinetic analysis is performed by noncompartmental (model independent) or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models.

Noncompartmental PK Analysis

Noncompartmental PK analysis is highly dependent on estimation of total drug exposure. Total drug exposure is most often estimated by Area Under the Curve methods, with the trapezoidal rule (numerical differential equations) the most common area estimation method. Due to the dependence of the length of 'x' in the trapezoidal rule, the area estimation is highly dependent on the blood/plasma sampling schedule. That is, the closer your time points are, the closer the trapezoids are to the actual shape of the concentration-time curve.

Compartmental PK Analysis

Compartmental PK analysis uses kinetic models to describe and predict the concentration-time curve. PK compartmental models are often similar to kinetic models used in other scientific disciplines such as chemical kinetics and thermodynamics. The advantage of compartmental to noncompartmental analysis is the ability to predict the concentration at any time. The disadvantage is the difficulty in developing and validating the proper model. The simplest PK compartmental model is the one-compartmental PK model with IV bolus administration and first-order elimination.

Bioanalytical Methods

Bioanalytical methods are necessary to construct a concentration-time profile. Chemical techniques are employed to measure the concentration of drugs in biological matrix, most often plasma. Proper bioanalytical methods should be selective and sensitive.

Mass Spectrometry

Pharmacokinetics is often studied using mass spectrometry because of the complex nature of the matrix (often blood or urine) and the need for high sensitivity to observe low dose and long time point data. The most common instrumentation used in this application is LC-MS with a triple quadrupole mass spectrometer. Tandem mass spectrometry is usually employed for added specificity. Standard curves and internal standards are used for quantitation of usually a single pharmaceutical in the samples. The samples represent different time points as a pharmaceutical is administered and then metabolized or cleared from the body. Blank or t=0 samples taken before administration are important in determining background and insuring data integrity with such complex sample matrices. Much attention is paid to the linearity of the standard curve; however it is not uncommon to use curve fitting with more complex functions such as quadratics since the response of most mass spectrometers is less than linear across large concentration ranges.[3][4][5]

There is currently considerable interest in the use of very high sensitivity mass spectrometry for microdosing studies, which are seen as a promising alternative to animal experimentation.

See also

References

  1. Leo A, Hansch C, and Elkins D (1971). "Partition coefficients and their uses". Chem Rev 71 (6): 525-616. doi:10.1021/cr60274a001.
  2. Kubinyi H (1979). "Nonlinear dependence of biological activity on hydrophobic character: the bilinear model". Farmaco [Sci] 34 (3): 248-76. PMID 43264.
  3. Increasing Speed and Throughput When Using HPLC-MS/MS Systems for Drug Metabolism and Pharmacokinetic Screening, Y. Hsieh and W.A. Korfmacher, Current Drug Metabolism Volume 7, Number 5, 2006, Pp. 479-489
  4. Covey TR, Lee ED, Henion JD. 1986. High-speed liquid chromatography/tandem mass spectrometry for the determination of drugs in biological samples. Anal Chem 58:2453-2460.
  5. Thermospray liquid chromatography/mass spectrometry determination of drugs and their metabolites in biological fluids. Covey TR et al. Anal Chem. 1985 Feb;57(2):474-81

External Links

Cost Effectiveness of Pharmacokinetics

| group5 = Clinical Trials Involving Pharmacokinetics | list5 = Ongoing Trials on Pharmacokinetics at Clinical Trials.govTrial results on PharmacokineticsClinical Trials on Pharmacokinetics at Google


| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Pharmacokinetics | list6 = US National Guidelines Clearinghouse on PharmacokineticsNICE Guidance on PharmacokineticsNHS PRODIGY GuidanceFDA on PharmacokineticsCDC on Pharmacokinetics


| group7 = Textbook Information on Pharmacokinetics | list7 = Books and Textbook Information on Pharmacokinetics


| group8 = Pharmacology Resources on Pharmacokinetics | list8 = AND (Dose)}} Dosing of PharmacokineticsAND (drug interactions)}} Drug interactions with PharmacokineticsAND (side effects)}} Side effects of PharmacokineticsAND (Allergy)}} Allergic reactions to PharmacokineticsAND (overdose)}} Overdose information on PharmacokineticsAND (carcinogenicity)}} Carcinogenicity information on PharmacokineticsAND (pregnancy)}} Pharmacokinetics in pregnancyAND (pharmacokinetics)}} Pharmacokinetics of Pharmacokinetics


| group9 = Genetics, Pharmacogenomics, and Proteinomics of Pharmacokinetics | list9 = AND (pharmacogenomics)}} Genetics of PharmacokineticsAND (pharmacogenomics)}} Pharmacogenomics of PharmacokineticsAND (proteomics)}} Proteomics of Pharmacokinetics


| group10 = Newstories on Pharmacokinetics | list10 = Pharmacokinetics in the newsBe alerted to news on PharmacokineticsNews trends on Pharmacokinetics</small>


| group11 = Commentary on Pharmacokinetics | list11 = Blogs on Pharmacokinetics

| group12 = Patient Resources on Pharmacokinetics | list12 = Patient resources on PharmacokineticsDiscussion groups on PharmacokineticsPatient Handouts on PharmacokineticsDirections to Hospitals Treating PharmacokineticsRisk calculators and risk factors for Pharmacokinetics


| group13 = Healthcare Provider Resources on Pharmacokinetics | list13 = Symptoms of PharmacokineticsCauses & Risk Factors for PharmacokineticsDiagnostic studies for PharmacokineticsTreatment of Pharmacokinetics

| group14 = Continuing Medical Education (CME) Programs on Pharmacokinetics | list14 = CME Programs on Pharmacokinetics

| group15 = International Resources on Pharmacokinetics | list15 = Pharmacokinetics en EspanolPharmacokinetics en Francais

| group16 = Business Resources on Pharmacokinetics | list16 = Pharmacokinetics in the MarketplacePatents on Pharmacokinetics

| group17 = Informatics Resources on Pharmacokinetics | list17 = List of terms related to Pharmacokinetics


}}ca:Farmacocinètica cs:Farmakokinetika da:Farmakokinetik de:Pharmakokinetiklt:Farmakokinetika nl:Farmacokinetiek no:Farmakokinetikksv:Farmakokinetik th:เภสัชจลนศาสตร์


Navigation WikiDoc | WikiPatient | Up To Date Pages | Recently Edited Pages | Recently Added Pictures

Table of Contents In Alphabetical Order | By Individual Diseases | Signs and Symptoms | Physical Examination | Lab Tests | Drugs

Editor Tools Become an Editor | Editors Help Menu | Create a Page | Edit a Page | Upload a Picture or File | Printable version | Permanent link | Maintain Pages | What Pages Link Here
There is no pharmaceutical or device industry support for this site and we need your viewer supported Donations | Editorial Board | Governance | Licensing | Disclaimers | Avoid Plagiarism | Policies
Linked-in.jpg