JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D IV Year BIOPHARMACEUTICS AND PHARMACOKINETICS Previous Question Paper (November/December - 2021 - R08)

Drug distribution is the reversible transfer of a drug between the blood and the extravascular fluids and tissues of the body. Phase I reactions, also known as functionalization reactions, involve the introduction or unmasking of a polar functional group (such as -OH, -NH2, -SH, or -COOH) on the drug molecule. These reactions typically increase the drug's hydrophilicity, making it more suitable for subsequent conjugation. The primary Phase I reactions are oxidation (catalyzed by cytochrome P450 enzymes), reduction, and hydrolysis.

Protein and tissue binding significantly influence the pharmacokinetics and pharmacodynamics of a drug. The key aspects include:

• Pharmacological Activity: Only the free (unbound) drug is pharmacologically active and capable of crossing membranes to reach the site of action.
• Distribution: Binding acts as a reservoir; as free drug is eliminated, bound drug dissociates to maintain equilibrium, thereby prolonging the drug's duration of action.
• Elimination: Highly protein-bound drugs are restricted from glomerular filtration, which can significantly decrease the rate of renal excretion.
• Drug Interactions: Drugs with high affinity for the same binding sites (e.g., albumin) can displace one another, leading to a sudden increase in the free concentration of the displaced drug, potentially causing toxicity.
• Tissue Storage: Accumulation in specific tissues (like fat or bone) can lead to localized toxicity or serve as a deep compartment that affects the volume of distribution.