Bioavailability of drugs (Distribution)

It is the fraction of a drug that reaches the systemic circulation from a given dose. The intravenous route of drug administration gives 100% bioavailability, as it directly enters the circulation. The term bioavailability is used commonly for drugs given by the oral route.

If two formulations of the same drug produce equal bioavailability, they are said to be bioequivalent.

If formulations differ in their bioavailability, they are said to be bio-inequivalent.

Factors Affecting Bioavailability

The factors that affect drug absorption (physicochemical properties of the drug, route of drug administration, pH and ionization, food, presence of other drugs, pharmacogenetic factors, area of absorbing surface, gastrointestinal and other diseases) also affect the bioavailability of a drug. Other factors that affect the bioavailability of a drug are discussed as follows:

1. First-pass metabolism (First-pass effect, systemic elimination): When drugs are administered orally, they have to pass via gut wall to the portal vein to the liver to the systemic circulation. During this passage, certain drugs get metabolized and are removed or inactivated before they reach systemic circulation. This process is known as first-pass metabolism. The net result is a decreased bioavailability of the drug and diminished therapeutic response. Drugs are lignocaine (liver), isoprenaline (gut wall), etc.

Consequences of high first-pass metabolism:

i. Drugs that undergo extensive first-pass metabolism are administered parenterally, e.g. lignocaine is administered intravenously in ventricular arrhythmias.

ii. Dose of a drug required for oral administration is more than that given by other systemic routes, e.g. nitroglycerin.

2. Hepatic diseases: They result in a decrease in drug metabolism; thus increasing the bioavailability of drugs that undergo first-pass metabolism, e.g. propranolol and lignocaine.

3. Enterohepatic cycling: It increases the bioavailability of drugs, e.g. morphine and doxycycline.