Anaes · Applied cardiovascular & respiratory physiology

ADME and routes of drug administration

Also known as ADME · Absorption distribution metabolism excretion · Routes of administration · Bioavailability · First-pass metabolism · pH partition hypothesis

ADME — absorption, distribution, metabolism and excretion — is the pharmacokinetic backbone that determines how much of a drug reaches its site of action, how quickly, and how long it stays. The route of administration sets the starting point of that journey and is one of the most important practical decisions in anaesthetic practice. The framework rests on six exam-critical ideas. First, the four ADME processes are sequential and interactive: a drug must be absorbed into the systemic circulation (unless given intravenously), distributed to its site of action, metabolised (chiefly by the liver) to a more water-soluble form, and excreted (chiefly by the kidney). Second, bioavailability is the fraction of the administered dose that reaches the systemic circulation unchanged; it is 1.0 (100 percent) for an intravenous dose and is reduced for oral drugs by incomplete absorption and by first-pass (presystemic) metabolism in the gut wall, the portal blood and the liver, which is why an oral dose is almost always larger than the equivalent intravenous dose. Third, the common routes differ sharply in onset and bioavailability: intravenous is instantaneous and complete (100 percent bioavailability) but irreversible; intramuscular and subcutaneous are near-complete and take minutes; inhalational is rapid (the lung is a superb absorption surface with a huge area and thin barrier) and titratable; oral is convenient but slow and limited by first-pass metabolism; transdermal is slow and sustained; sublingual and intranasal bypass first-pass metabolism. Fourth, absorption across a biological membrane depends on surface area, blood flow, and most fundamentally on the drug's ionisation — only the unionised (lipid-soluble) fraction crosses lipid membranes, described by the pH partition hypothesis and the Henderson-Hasselbalch equation. Fifth, drug metabolism occurs in two phases: Phase I (oxidation, reduction, hydrolysis, chiefly by the cytochrome P450 superfamily) which often unmasks or introduces a functional group, and Phase II (conjugation with glucuronide, sulphate, acetate or glutathione) which makes the molecule more water-soluble for excretion; many drugs are administered as inactive prodrugs that require Phase I or II conversion to their active form. Sixth, excretion is mainly renal (glomerular filtration, active tubular secretion, and passive tubular reabsorption that is pH-dependent) and biliary, with enterohepatic recirculation prolonging the action of some drugs. Built on the oral S-ketamine pharmacokinetic study (van Mechelen 2026), the CYP450 metaboliser phenotype study (Oskay 2026), the subcutaneous absorption modelling review (Siemiątkowska 2026), the transdermal patch permeation study (Garg 2026), the mycophenolic-acid enterohepatic-recirculation report (Śmiertka 2026), the intranasal administration review (Jafarbeglou 2026), the intestinal-fluid solubilisation and lipophilicity study (Boyanov 2026), and the renal-impairment pharmacokinetic study (Kojima 2026).