phrmacokinetics bds

8/14/2019 Phrmacokinetics BDS

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Dr.U.P.RathnakarDr.U.P.Rathnakar

MD.DIH.PGDHMMD.DIH.PGDHM

a1


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PK is the quantitative studyof drug movement in,

through and out of thebody

During these processes the

drug has to cross variousbiological membranes


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PK-Membrane Transport

Mechanism by which drugs cross biological membrane


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Membrane Transport..

Passive diffusion and Filtration

Specialized transport

Carrier transport

Facilitated diffusion Active transport

Pinocytosis


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PaPassive diffusionssive diffusion Bidirectional process, Movement of molecules from

higher to lower conc [Down the gradient]

Lipid soluble drugs- Passive diffusion, afterdissolving in the lipid of cell membrane

Acidic drugs are unionized in acidic medium

Alkaline drugs are unionized in alkaline Medium

Unionized drugs are readily absorbed More lipid soluble Diffuses quickly

Greater the difference in concn gradient

Quicker diffusion

Ion trappingUrine alkalanizedin poisoning withacidic drugs


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Filtration


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FILTRATION

Capillaries (Except in brain-Tightjunction) have large pores & most

drugs filter through these.Lipid insoluble drugs cross

biological membranes byfiltration through these pores

Diffusion of drugs is dependent onRate of Blood Flow


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Specialized transport: Carrier mediated Drug + CARRIER in the membrane complex is

transported from one side of the membrane to other.

Eg. Calcium & iron absorption Carrier transport

1. Specific,

2. Saturable,3. Competitively inhibited by - which utilize the same

carrier.


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Specialized transport: Carrier mediated

Facilitated diffusion

No energy required Drug + carrier[SLC Transporter] in the

membrane, diffusion across the cell

membrane.

Movement ONLY higher to lower conc[ALONG]

Eg. Vit. B12 absorption


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Specialized transport: Active transport

Movements of molecules Low

conc. To high conc.Against the conc.gradient

Require energy.

P-glycoprotein


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Specialized transport Active transport:Primary

Primary Active Transport

ATP Binding Cassette-

Transporter

Only out of the cytoplasm

Energy derived from ATP


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Specialized transport Active transport

:Secondary:

Energy derived from movement of anothersubstance

In the same direction-Symport

In opp.direction -Antiport

Pinocytosis; By formation of vesicles


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Membrane Transport..Facilitated diffusion

Primary active

Secondary active- Symport

Secondary active-Antiport


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Absorption

[Movement from site of administration tocirculation]

ORAL:

S.c, i.m: Absorbed by capillaries or lymphatics

Topical: Lipid solubility-Hyoscine, Fentanyl, GTN,

Nicotine, Testosterone, Estradiol

Cornea


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BA=30/150

First pass metabolism


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Absorption: Bio-Availability The fraction [F] of administered dose of a drug that

reaches systemic circulation in the unchanged form

I.V. 100% Bio-availablity

Oral-Not 100%. WHY?1. Incompletely absorbed

2. First pass metabolism

i.m or s.c. also may be lessthan 100% -Local binding


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Absorption:Factors

Aqueous solubility

Concentration

Area of absorbing surface Vascularity

pH and ionization

Food Other drugs

Diseases

Route


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DISTRIBUTION

Reversible transfer of drugsbetween body fluid compartments

After absorption drug entersvarious body fluid compartments.

Plasma Interstitial fluid compartment

Cellular fluid compartment.


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Drug enters body

Plasma compartment:Large mol.wt.Bound to plasma proteinsCannot cross capillariesRemains trapped in vascularcompartment [4L]

Extracellular fluid:Low mol.wt.HydrophilicCan cross capillaries(Slit junc)Can not enter cells(Crossplasma membrane-Not lipidsoluble)Remains inPlasma+InterstitiaL fluid[14L]

Total body water:Low mol.wt.HydrophobicCan cross capillariesCan enter cells(Cross plasma membrane)Distrbutes in vol. of 60% ofbody wt.[42L]

Other sites:In pregnancy-FetusFat-Thiopental

Usually drugs not confined

One compt.


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Drug in beaker Drug + Charcoal in beaker

Drug=10mgConcn=20mg/LaVD=10/20mg/L

=500ml=Vol.of

beaker

Drug=10mgConcn=2mg/LaVD=10/2mg/L

=5000ml=Muchmore thanVol.ofBeakerand charcoal

Apparent Volume of Distribution


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Apparent volume of distribution aVD: The volume that would accommodate all thedrug in the body, if the concn.throughout was thesame as in plasma

Lipid insoluble: Small aVD-Eg.Gentamicin-.25L/kg

Highly protein bound-Eg.Diclofenac-0.15L/kg.

Highly tissue bound-Eg.Morphine-3.5L/kg

High vol. of distribution-poisoning-difficult toremove by dialysis


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Redistribution

Highly lipid solubleThiopentone-i.v

Distributed toorgans with high

blood flow.

Eg.Brainsite ofaction

Unconcious

Less vascularareasEg.Fat,muscle

Plasmaconcn.falls

Concious[Drug

withdrawnfrom

brain]

Redistribution

10Sec

10Mts


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Blood Brain Barrier

BBB ONLY Lipid soluble and unionized drugs cross

Anesthetics, Barbiturates

Meningitis increase permeability- Impermiablesubstances Cross!


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Placental barrier Bet.mother and fetus Lipid soluble and unionized cross-anesthetics, alcohol

High mol.wt.do not-insulin Teratogenicity ( Teratos = Monster) Tetracyclines, Thalidomide Anti-cancer drugs, Sex

hormones


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l b


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Plasma protein binding

Drug

ABSORPTION

Enters circulation

Binds to plasma proteins

[acidic to albumin, basic to a-acidglycoprotein]

Bound- inactiveTemp. storage site,Long duration,Hemodialysis noteffective

Freeform-

Active


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Plasma protein binding: Clinical Imp.

Favors drug absorption

Affects Vd

Delays metabolism, excretion,

Not available for actionStorage site

Displacement reactions-


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