Our Latest eNews
ANTIHYPERLIPIDEMIA AGENTS Plasma lipids Transported in bloodstream in form of macromolecular complexes of lipid and known as lipoproteins Two major clinical importance/sequelae of high lipid Acute pancreatitis atherosclerosis Hyperlipoproteinemia Hyperlipidemia Lipoprotein disorders Primary hypertriglyceridemias Primary chylomicronemia Familial hypertriglyceridemia Familial combined hyperlipoproteinemia Familial dysbetalipoproteinemia Primary hypercholesterolemias Famimial hypercholesterolemia Familial ligan-defective apolipoprotein B Familial combine hyperlipoproteinemia Lp(a) hyperlipoproteinemia Secondary hyperlipoproteinemia Lipid-lowering drugs Several drugs are used To decrease plasma LDL-cholesterol Drug therapy is only one approach Dietary measures are the first [...] | 19th January, 2010 | More News
Pharmacokinetic Parameters
Excretion of drug (Major)
It is the passage out of drug from body.
Urine
Most drugs
Most important channelvia Kidney
Faeces
Unabsorbed fraction of drug
In the bile
via liver metabolism
Molecular weight > 300
Eg heavy metals
Exhaled air
Gases
Volatile liquids - alcohol
Excretion of drug (minor)
Saliva and sweat
Eg Lithium
Potassium iodide
Thiocyanates
Rifampin
Milk
Drug enter breast milk by passive diffusion
Lipid soluble drug
Less protein binding
Basic drug – milk is more alkaline
List of drugs that are contraindicated during breast feeding?
Eg. Chloramphenicol – bone marrow depression
Iodine
Renal excretion
Kidney
Excretes all water soluble substances
Drug undergoes
Glomerular filtration
Tubular reabsorption
Tubular secretion
Kinetics of elimination
Provides
Rational dosage regimes
To modify dosage according to individual needs
Three fundamental of pharmacokinetic parameters
Bioavailability (F)
Volume of distribution (V)
Clearance (CL)
Drug elimination
Equilibration between the central compartment (Blood) and peripheral compartments (site of action, storage tissue)
Clearance (CL)
Is a removal of drug completely in a unit time of the theoretical volume of plasma.
CL = Rate ofelimination/C
C is the plasma concentration
Rate of elimination
Majority of drugs follow the First order (exponential) kinetics or zero (linear) order kinetics
First order (exponential) kinetics
Elimination of drug are not saturated over the clinically obtained concentration
Rate of elimination is directly proportional to drug concentration
Clearance - constant
zero (linear) order kinetics
Elimination of drug are saturated over the clinically obtained concentration
Rate of elimination constant irrespective of drug concentration
Plasma half-life (t 1/2)
The time taken for its plasma concentration to be reduced to half of its original value.
Eg. 1 t ½ - 50% drug is eliminated
2 t ½ - 75% (50+25) drug is
eliminated
3 t ½ - 87.5% (50+25+12.5) drug is
eliminated
4 t ½ - 93.75% (50+25+12.5+6.25)
drug is eliminated
Therefore, for nearly complete drug elimination, its needs 4-5 half-life
Plasma half life
Aspirin – 4 hours
Doxycycline – 20 hours
Digoxin – 40 hours
Digitoxin – 7 days
Repeated drug administration
Drug is repeated at relatively short intervals
It accumulates until it reached
Elimination balances input
Steady state plasma concentration (Cpss)
Loading dose vs maintenance dose
Loading dose is a single or few quickly repeated doses given in the beginning of treatment to attain the target concentration rapidly.
Maintenance dose is repeated doses given at specific intervals after the attainment of target Cpss
Therapeutic drug monitoring
Drug with low safety margin
Eg lithium, anticonvulsants drugs
Individual variations are large
Lithium
Potentially toxic drugs used
Use of drug in renal failure patient
Drug poisoning
Suicidal, suspected homicidal
Drug response
Failure of treatment
Patient compliance
Psychiatric treatment
Formulation and modification of drug
Advantages of prolongation of drug action
Reduces the frequency of administration
Improves patient compliance towards drug intake
Avoids Large fluctuations effects
Side effects related to high peak plasma level
What are the methods to prolong drug action?
Referances
Essentials od medical pharmacology, KD Tripathi
Pharmacology, katzung
About the Author
Specialized in Tropical Medicine and Research on men health especially in osteoporosis