Pathophysiology
Clinical meaning
Pharmacokinetics describes how the body handles a drug through four processes: absorption, distribution, metabolism, and elimination (ADME). Absorption is the movement of a drug from its site of administration into the systemic circulation, governed by the drug's lipophilicity, molecular size, ionization state (Henderson-Hasselbalch equation), and the surface area and blood flow at the absorption site. Oral drugs are absorbed primarily in the small intestine (large surface area from villi and microvilli) and must cross the intestinal epithelium via passive transcellular diffusion (lipophilic drugs), paracellular transport (small hydrophilic molecules), or active carrier-mediated transport (e.g., levodopa via amino acid transporters). Bioavailability (F) is the fraction of an administered dose that reaches the systemic circulation unchanged โ IV administration has 100% bioavailability by definition, while oral bioavailability is reduced by incomplete absorption, intestinal metabolism (CYP3A4 in enterocytes), efflux pumps (P-glycoprotein returning drug back into the gut lumen), and first-pass hepatic metabolism. First-pass metabolism occurs when orally absorbed drugs travel via the portal vein to the liver before reaching systemic circulation; hepatic enzymes (predominantly cytochrome P450 isoenzymes โ CYP3A4 metabolizes approximately 50% of all...