It is the movement of the drug and the effect of the body on the drug. The pharmacokinetics deals with the absorption, distribution, metabolism and excretion of a drug.
Absorption - By oral, the drug should cross the membrane of GIT and blood vessels to reach the blood and it should be in lipid-soluble form. Lipid soluble form of drugs are absorbed in un-ionized form and the ionized form is water-soluble. Most drugs are absorbed in Un-ionized form. The volume of distribution(Vd) reflects the amount of drug distribution in the tissues. Chloroquine is the drug with the highest Vd. Acidic drugs bind to albumin and basic drugs bind to alpha-1 acid glycoprotein. The volume of distribution is decreased if a drug has a high plasma protein binding. Acidic drugs will be absorbed in the stomach and in the un-ionized form. eg. Aspirin.
If the pH of the medium is less than Pka, the medium becomes acidic, i.e. acidic drugs in more un-ionized form and basic in more ionized form and vice-versa, if the pH of the medium is more than pKa. The pH is calculated by the Henderson-Hasselbach equation,
i.e. pH=pKa + log(protonated form/unprotonated form).
The oral drugs will undergo high first-pass metabolism in the liver and intestinal wall and rectal route drugs will avoid 50% of the first-pass metabolism. The term bioavailability is the amount of administered drug that enters the systemic circulation in its original form. The bioavailability of intravenous route drugs is 100%. The examples of drugs with high first-pass metabolism are Hydrocortisone, Morphine, Lignocaine, Propranolol, salbutamol.
Distribution - Several factors like lipid solubility and plasma protein binding will determine the volume of distribution(Vd). If a drug enters more in the tissue, it has a higher volume of distribution(Vd). Lipid soluble drugs have a high volume of distribution when compared with plasma protein binding drugs. The drugs and their poisoning which have a low volume of distribution can be treated well with dialysis, the exceptions are digoxin, beta-blockers, calcium channel blockers, antidepressants, antipsychotics, amphetamines, opioids, benzodiazepines, quinidine. The drugs which have high plasma protein binding cannot be removed by dialysis because dialysis will not filter proteins. Dialysis will not be effective for drug poisons like organophosphates, opioids, diazepam, verapamil, etc.
Metabolism - The primary site is liver. Prodrugs mean the inactive form of the drug will be active compound after metabolism. eg. Methyldopa, levodopa, clopidogrel, etc. Enzyme inducers will increase the metabolism of the drug and their effect will be decreased.eg- Rifampicin, Phenytoin, Phenobarbitone, Griseofulvin, carbamazepine, etc. Enzyme inhibitors will decrease the metabolism of drugs. eg- Erythromycin, Metronidazole, ketoconazole and cimetidine. Such drugs are metabolized by microsomal enzymes. Examples of microsomal enzymes are cytochrome P450, Flavin monooxygenases, glucuronide conjugation, reduction and hydrolysis.
Excretion - The drugs are excreted through kidney by glomerular filtration, tubular reabsorption and tubular secretion. Rifampicin, Lithium is secreted in saliva.
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