A for Absorption !

Absorption is the movement of drug from its site of administration into the circulation. Not only the fraction of the administered dose that gets absorbed, but also the rate of absorption is important. 

Routes of drug administration and absorption of drugs (sr: Rang and Dale's Pharmacology)

Except when given intravenous, the drug has to cross biological membranes. Other factors influencing absorption are:

• Aqueous solubility : Drugs given in the solid form must dissolve in aqueous biophase before they are absorbed. A drug given as watery solution is absorbed faster. 
• Concentration : Passive diffusion depends on concentration gradient : concentrated drug solution is absorbed faster.
• Area of absorbing surface: Larger it is, faster the absorption.
• Vascularity of the absorbing surface : Blood circulation removes drug from site of absorption and maintains concentration gradient.
• Route of administration : Main routes include oral, sublingual, rectal, topical application, inhalation, injections etc. Each route has its own peculiarities.

Let's take the case of Oral route of drug administration. 

The effective barrier to orally administered drugs is the epithelial lining of the GI tract (lipoidal).

• Nonionised lipid soluble drugs ( like ethanol) --> readily absorbed from intestine and stomach
• Acidic drugs ( e.g. salicylates, barbiturates ) --> mostly unionised in acid gastric juice --> absorbed from stomach.
• Basic drugs (e.g. morphine, quinine ) --> largely ionised in stomach --> absorbed in the intestine

Absorption of drugs from the intestine as a function of pKa for acids and bases (sr: Rang and Dale's pharmacology)

• Dissolution : a surface phenomenon --> particle size of drug in solid dosage form governs the rate of dissolution and thus in turn the rate of absorption.
• Faster gastric emptying accelerates drug absorption in general.
• Presence of food dilutes the drug and retards absorption, also delays gastric emptying.
• Highly ionised drugs (e.g. gentamicin ) --> poorly absorbed.
• Certain drugs --> degraded in the GI tract : e.g. insulin by peptidases --> ineffective orally.
• Low absorption of certain drugs --> fraction of the absorbed drug is extruded back into the intestinal lumen by efflux transporter P-gp in the gut epithelium (e.g. partial cause of low bioavailability of digoxin).
• Absorption affected by other concurrently ingested drugs --> luminal effect : formation of insoluble complexes (e.g. phenytoin with sucralfate)

BINDING OF DRUGS TO THE PLASMA PROTEIN

Many drugs possess physiochemical affinity for plasma proteins. Fraction of drug free in the aqueous solution  < 1% --> unbound drug --> pharmacologically active.

• Most important plasma protein - Albumin --> binds to many acidic drugs (e.g. warfarins); smaller no. of basic drugs (e.g. chlorpromazine).
• Other plasma proteins : beta- globulin, alpha-1- acid glycoprotein 

Increasing concentrations of the drug can progressively saturate the binding sites : fractional binding may be lower when large amounts of the drug are given.