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

Factors influencing gastrointestinal drug absorption include physiological factors (gastrointestinal pH, gastric emptying rate, intestinal motility, blood flow, and presystemic metabolism) and physicochemical factors (drug solubility, dissolution rate, particle size, polymorphism, salt form, and lipophilicity).

The pH-partition hypothesis states that the absorption of drugs across the gastrointestinal membrane is governed by the pKa of the drug, the pH of the environment, and the lipid solubility of the unionized form. According to this hypothesis, only the unionized, lipid-soluble form of a drug can permeate the lipid bilayer of the intestinal membrane by passive diffusion. The ratio of unionized to ionized drug is determined by the Henderson-Hasselbalch equation:

Weak acids are primarily unionized in the acidic environment of the stomach and are absorbed there, while weak bases are primarily unionized in the more alkaline environment of the small intestine, making the intestine the primary site for their absorption.

Renal excretion is the primary route for the elimination of drugs and their metabolites. It involves three fundamental processes occurring in the nephron:

• Glomerular Filtration: Drugs with a molecular weight less than 60,000 Daltons that are not bound to plasma proteins are filtered from the blood into the Bowman's capsule. This is a passive, non-selective process driven by hydrostatic pressure.
• Active Tubular Secretion: This process occurs primarily in the proximal tubule and involves carrier-mediated transport systems. It is an energy-dependent process that can transport drugs against a concentration gradient, allowing for the secretion of both acidic and basic drugs, even those bound to plasma proteins.
• Tubular Reabsorption: As the filtrate passes through the distal tubule, lipid-soluble, unionized drugs may be reabsorbed back into the systemic circulation by passive diffusion. This process is pH-dependent; altering urinary pH can significantly influence the reabsorption rate, a principle used in treating drug overdoses by ion-trapping.