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2nd October, 2009
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Absorption and Distribution

Posted by tajul (Doctor) on 2nd October, 2009, in Education Study, Medical science, Medicine, Pharmacy

Pharmacokinetics - WTBDTTD
Quantitative study of drug movement:
In
Through of the body
Out
 

•It is dealing with the dose-concentration part
•three primary processes of pharmacokinetics are
–absorption,
–distribution, and
–elimination
•It determine
–how rapidly and
–for how long the drug will appear at the target organ.
»Katzung (9th edition)

Principles of Pharmacokinetic
a drug should be able to reach its intended site of action after being administrated.
prodrug - a chemical that is readily absorbed and distributed and then converted to the active drug by biologic processes in the body.
direct application of drug to its target tissue, eg, by topical application to inflamed skin or mucous membrane.
administered into one body compartment and move to another compartment for their action.
drug absorbed into the blood and distributed to its site of action.
permeating through the various barriers that separate these compartments.
Finally, eliminated from body by
Excretion, or
Metabolic inactivation, or combination of these processes.
Pharmacokinetic processes
Administration Route
Oral, Inhale, Parentrel etc
Absorption
Site
Factors affecting absorption
1.Aqueous solubility, 2.Concentration, 3.Area of absorbing surface, 4.route of administration
Distribution
Distributed by concentration gradient in direction of plasma to tissue.
Factors affecting Distribution 1.lipid solubility, 2.ionization at physiological pH, 3.extent of binding to plasma and tissue proteins, 4.differences in regional blood flow
Redistribution, placenta passage, Penetration into brain and CSF, Plasma protein binding
Storage
Drugs accumulation and binding to specific organ or tissue
Eg digoxin –heart tissue/skeletal muscle/kidney
Iodine – thyroid
Chloroquine – iris, liver, kidney
Tetracycline – bone and teeth
Biotransformation (metabolism)
Inactivation, Active metabolite from an active drug, Activation of inactive drug (Prodrug), Nonsynthetic/synthetic reactions, inhibition of drug metabolism, microsomal enzyme induction, first pass methabolism
Excretion
Urine, Faeces, exhale air, saliva and sweat, milk, renal

 Absorption

 Is the movement of drug from its site of administration into the circulation.
 
Factors affecting absorption
  
1.Aqueous solubility – solid form < watery solution. Solid drug have to dissolve in the aqueous before being absorbed.
2.Concentration – concentrated drug solution is absorbed faster than diluted drug solution
3.Area of absorbing surface. Large > small surface area eg. Intestine wall surface area > stomach surface area
1.Slow absorption from stomach
1.Thick mucus covered mucosa
2.Small surface area
4.Blood supply to the absorbing area. Increased blood supply > absorption rate
5.Route of administration
 
•Oral
–Effective barrier is gastrointestinal tract lining epithelial
–It is lipoidal
–Nonionized lipid soluble drugs are easily absorbed from stomach and intestine eg. Ethanol
–An acidic drugs are absorbed in stomach. They predominantly unionized in gastric juice. Eg. Phenobarbital, Penicillin G (Penicillin G Potassium)
–Basic drugs are absorbed in duodenum. They are ionized drugs. Eg. Tetracycline (Tetracycline HCl)
–Stomach contents – food particle reduces the absorption
–Stomach emptying time – faster emptying time accelerates drug absorption.
 
•Subcutaneous and intramuscular
–Drugs are administrated directly into the tissues where the capillaries are situated
–Increased the drug absorption even that of lipid insoluble molecules.
–Increased blood flow to the tissues will accelerate absorption eg exercise

–

Vasoconstriction of blood vessels reduces the absorption.

  Topical application

Only few drugs able to penetrate skin eg. Nitroglycerine, Corticosteroids

–The drugs are lipid soluble

–
Bioavailability
 
•Measure the fraction of drugs of administration dose in unchanged form that reach the systemic circulation
•Intravenous (I.V.) – 100%
•Oral - < 100%
–Incomplete absorption
–First pass metabolism
•Different drugs may have different bioavailability even though have same chemical.
 
Distribution
  
•After drugs administration via various route, it will get distributed to the tissues by concentration gradient
•Movement of drugs will continue until it reaches an equilibrium between unbound drug in plasma and tissue fluids
•Subsequent parallel decline due to elimination
 
Factors influence the distribution of drugs
  
•Lipid solubility
•Ionization at physiological pH (dependent on pKa)
•Extent of binding to plasma and tissue proteins
•Differences in blood flow of the area

 

 

 

 

About the Author

tajul Specialized in Tropical Medicine and Research on men health especially in osteoporosis

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