dr.soban sadiq. pharmacokinetics absorption distribution metabolism(biotransformation) excretion

DR.SOBAN SADIQ

PharmacokineticsAbsorptionDistributionMetabolism(Biotransformation)Excretion

Routes of drug administrationEnteral(Through Alimentary tract)Oral Sublingual or buccalRectalParenteral(Through Injection)IntravenousIntramuscularSubcutaneous

IntradermalIntraperitonealIntrapleuralIntracardiacIntra-arterialIntrathecalIntra-articular

Absorption is the transfer of a drug from its site of administration to the blood stream.

Factors affecting drug absorption:

1-Lipid-water partition co-efficient: Non electrolyte drug depends upon lipid solubility.

More lipid soluble and less water soluble that is it has high lipid-water partition co-efficient, it will absorbed rapidly

2- Drug solubility: drugs given in aqueous solutions are more rapidly soluble than when given in oily solution, suspension or solid form.

3- Dosage form: Tablets and capsules, rate of disintegration and dissolution is limiting factor in their absorption. After dissolution, smaller the particle size, more efficient will be absorption

4- Circulation at the site: Increased blood flow increase absorption

How blood flow increase?How blood flow decrease?

5- Area of absorbing surface : Absorbed more from large surface areas for example intestinal mucosa

6- Effect of pH: Most drugs are either weak acids or weak bases. Weak electrolytes, in addition to lipid solubility, depends upon its degree of ionization which is influenced by pH of the area.

Weak acids become less ionized(charged) in an acidic medium and weak bases become less ionized in an alkaline medium

Unionized drug is lipid soluble and diffusible

Acidic drug will absorb more in stomach or intestine?So,

Lipid soluble(hydrophobic), uncharged, unionized will cross the membrane rapidly than lipid insoluble(hydrophilic or water soluble),charged and ionized.

Basic drug will absorb more from intestine because it becomes unionized in basic medium. In acidic medium basic drug will become more ionized and thus no absorption will takes place.

Functional integrity of the GIT: Increased peristaltic activity as in diarrhea reduces drug absorption

Increased gastric emptying time, absorption will be more.

BioavailabilityThe fraction of unchanged drug reaching the systemic

circulation following administration by any route”

or

The percentage of administered drug that reaches the systemic circulation in a chemically unchanged form”

Thus by definition a drug that is administered by intravenous route has 100% bioavailability

Main organ of metabolism is liverSpecific drugs are metabolized in gut wall, skin,

lungs

Factors affecting bioavailability1-First-pass hepatic metabolism: when a drug is absorbed across GIT, it enters the

portal circulation before entering the systemic circulation.

If the drug is rapidly metabolized by the liver ,the amount of unchanged drug that gains access to the systemic circulation is decreased

2-AbsorptionSolubility of the drug: hydrophobic drug will absorb

more so bioavailability will be moreChemical instability: some drugs are unstable in pH

of the gastric contents. Others are destroyed in GIT by degradative enzymes e.g. insulin so bioavailability?

Particle size: smaller the particle size more absorption will be there. so bioavailability?

Plasma half lifeThe time required for the concentration of drug in the

plasma to decrease to one half of its initial value. for example if the initial conc. of drug is 100mg and

if the half life is 1 hr, only 50mg will remain in the plasma at the end of 1 hr.

Time : 0 1hr 2hr 3hr 4hr Cp (mg/dl): 100 50 25 12.5 6.25

So from this table we can deduce that the half-life of this drug is 1 hour.

ImportanceIt denotes how quicky a drug is removed from the

plasma by biotransformation or excretionSince drug require a minimum conc. in the plasma to

produce pharmacological action, a drug which is eliminated quickly requires more frequent dosing than a drug with a long half life.

It thus indicates the duration of action of drug and therfore it determines the frequency of administration of dose of the drug for therapeutic effectiveness.

Complete drug elimination occur in 4-5 half lives. After that drug will reach steady state concentration in the plasma.

(drug administered=drug eliminated)1-50 %2-75%(50+25)3-87.5%(50+25+12.5)4-93.75%(50+25+12.5+6.25)

1-Alkalinization of urine hastens the excretion of :

A-Weakly basic drugsB-Weakly acidic drugsC-Strong electrolytesD-Nonpolar drugs

2-Diffusion of drugs across cell membrane :

A-Is dependent upon metabolic activity of the cellB-Is competitively inhibited by chemically related

drugsC-Is affected by extent of ionization of drug

moleculesD-Exhibits saturation kinetics

3-The most important factor governing absorption of a drug from intact skin is :

A-Molecular weight of the drugB-Site of applicationC-Lipid solubility of the drugD- Nature of the base used in formulation

4-What kind of substances can’t permeate membranes by passive diffusion?

A- Lipid-solubleB- Non-ionized substancesC- Hydrophobic substancesD- Hydrophilic substances

Which route of administration of drug will provide highest bioavailability:

  A-SubcutaneousB-OralC-SublingualD-Rectal

Which route of drug administration is most likely lead to the first-pass effect?

a) Sublingualb) Oralc) Intravenousd) Intramuscular

Which of the following factor does not influence the oral bioavailability of the drugs

A-metabolism by gut wall enzymesB-Decomposition by hydrolytic gut enzymesC-Chelation with existing food in stomachD-Plasma half life