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 — 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 — CYP3A4 metabolizes approximately 50% of all drugs, CYP2D6 metabolizes 25%) biotransform the drug through Phase I reactions (oxidation, reduction, hydrolysis adding or exposing functional groups) and Phase II reactions (conjugation with glucuronic acid, sulfate, or glutathione to increase water solubility for renal excretion). Drugs with high hepatic extraction ratios have dramatically reduced oral bioavailability: nitroglycerin (>90% first-pass extraction, requiring sublingual administration), morphine (~70%, explaining why oral morphine doses are 3× IV doses), and propranolol (~75%). Volume of distribution (Vd) reflects a drug's tendency to distribute into tissues versus remaining in plasma — highly lipophilic drugs and drugs with extensive tissue binding have large Vd values. Half-life (t½ = 0.693 × Vd/Clearance) determines dosing frequency, and steady state is reached after approximately 4-5 half-lives of repeated dosing. Genetic polymorphisms in CYP enzymes create clinically significant variations: CYP2D6 poor metabolizers cannot convert codeine to its active metabolite morphine (therapeutic failure), while CYP2D6 ultra-rapid metabolizers produce excessive morphine (potentially fatal, especially in breastfeeding infants and children). Understanding these pharmacokinetic principles enables the NP to select appropriate drugs, routes, and doses tailored to individual patient physiology.