Pharmacokinetics is what the body does to a drug: absorption, distribution, metabolism and excretion (ADME). Pharmacodynamics is what the drug does to the body, from receptor binding to the effect you assess at the bedside. Together they explain how fast a dose works, how long it lasts and why kidney disease, liver disease or age can change the right dose.
Key takeaways
- An IV dose has 100% bioavailability by definition; oral doses often deliver less.
- Propranolol is almost completely absorbed, yet on average only about 25% reaches the circulation because of first-pass metabolism.
- For most drugs, 94% to 97% of a dose is gone after 4 to 5 half-lives, and regular dosing takes about 4 to 5 half-lives to reach steady state.
- Warfarin is about 99% protein-bound and cleared by liver CYP450 enzymes, so a new antibiotic or herbal product can move the INR.
- Digoxin’s half-life of 1.5 to 2 days stretches to 3.5 to 5 days when the kidneys produce no urine.
- After age 40, GFR falls about 8 mL/min/1.73 m² per decade on average, while serum creatinine often looks normal.
Pharmacokinetics vs Pharmacodynamics in One Sentence Each
Pharmacokinetics is the movement of a drug into, through and out of the body over time. Pharmacodynamics is the drug’s effect, mostly through binding to receptors. As the Merck Manual puts it, pharmacokinetics determines the onset, duration and intensity of an effect. The warfarin label uses the same split for interactions: pharmacokinetic ones work through enzyme induction, inhibition or reduced protein binding; pharmacodynamic ones through added effects on clotting.
| Feature | Pharmacokinetics | Pharmacodynamics |
|---|---|---|
| Short version | What the body does to the drug | What the drug does to the body |
| Key numbers | Bioavailability, half-life, clearance | Potency, efficacy, therapeutic index |
| You check | Drug levels, kidney and liver function | The response: blood pressure, pain, INR |
| Warfarin example | Fluconazole slows its metabolism | Aspirin adds bleeding risk |
Each stage below follows one drug, warfarin, using its FDA label. For a drug-card routine, see how to study pharmacology in nursing school.
Absorption in Pharmacokinetics: Routes, Bioavailability and First Pass
Absorption is the movement of a drug from where it’s given into the systemic circulation. The fraction that arrives is its bioavailability: 100% for an IV dose by definition, often less for oral doses (StatPearls).
Routes and bioavailability
Oral drugs face stomach acid and digestive enzymes, and most are absorbed in the small intestine. Fatty food slows gastric emptying and the rate of absorption, and low blood flow in shock can reduce it (Merck Manual). Routes aren’t interchangeable: digoxin tablets deliver about 60% to 80% of an identical IV dose, per the Lanoxin label.
First-pass effect
The first-pass effect is metabolism of an oral drug by the gut wall and liver before it reaches the systemic circulation (Merck Manual: Drug Bioavailability). Propranolol’s label says it is almost completely absorbed, yet only about 25% reaches the circulation. StatPearls lists morphine among drugs whose oral doses must be much larger than IV doses for this reason.
IV, sublingual, transdermal, inhaled and, largely, rectal routes avoid most first-pass loss. Sublingual nitroglycerin works in about 1 to 3 minutes, and its label tells patients to let the tablet dissolve without swallowing.
Essentially completely absorbed after an oral dose, with peak concentration usually within 4 hours. The complications come later.
Distribution: Where the Drug Goes
Distribution is the movement of drug from the blood into tissues. Blood flow, protein binding, fat or water solubility and barriers decide where it goes and how much is free to act (Merck Manual: Drug Distribution).
Protein binding
Only unbound drug can leave the blood, reach receptors and be filtered by the kidney. Acidic drugs bind mainly to albumin. When albumin falls from malnutrition, acute illness or liver disease, more drug is free, and Merck names phenytoin and warfarin as drugs with higher toxicity risk then. Volume of distribution (amount in body divided by plasma concentration) shows where a drug sits: about 0.14 L/kg for warfarin, which stays largely in plasma, versus roughly 475 to 500 L for tissue-bound digoxin.
Blood-brain barrier
Tightly joined capillary cells let lipid-soluble drugs into the brain while keeping most water-soluble ones out. Diphenhydramine crosses and causes drowsiness (Open RN). The barrier is still developing in infants and may leak more with aging, so both groups can get stronger CNS effects.
About 99% is bound to plasma proteins, so only a small free fraction acts. Its label lists reduced protein binding as one interaction route.
Metabolism: Liver Enzymes and Drug Interactions
Metabolism chemically changes a drug, usually into a water-soluble form the kidneys or bile can remove. The liver does most of it through phase I reactions, mainly CYP450 oxidation, and phase II conjugation (Merck Manual: Drug Metabolism). It doesn’t always inactivate: codeine is a prodrug that must be metabolized to work.
Liver enzymes and drug interactions
Enzyme inducers lower other drugs’ levels; inhibitors raise them. The warfarin label lists fluconazole, amiodarone and metronidazole as CYP2C9 inhibitors and rifampin and carbamazepine as inducers. The FDA warns that grapefruit juice blocks intestinal CYP3A4, letting more of some drugs, including certain statins, into the blood. Liver disease slows metabolism too: in a study cited in propranolol’s label, its half-life was 11 hours in cirrhosis versus 4 hours in healthy volunteers.
Cleared almost entirely by liver CYP450 enzymes, mainly CYP2C9. Its label calls for closer INR checks whenever an inhibitor or inducer, antibiotic, antifungal or botanical is started or stopped.
Excretion: Kidneys, Clearance and Dose Adjustment
Excretion removes a drug or its metabolites, mostly through the kidneys into urine, with smaller routes through bile, lungs and breast milk (Merck Manual: Drug Excretion). Only unbound drug is filtered.
Renal function and dose adjustment
Kidney function is estimated from serum creatinine, eGFR or creatinine clearance, often by the Cockcroft-Gault formula. Our NCLEX lab values cheat sheet covers the creatinine and BUN ranges. Digoxin is 50% to 70% excreted unchanged after an IV dose and needs smaller maintenance doses in kidney impairment. The lithium label advises lower starting doses at a creatinine clearance of 30 to 89 mL/min and doesn’t recommend it below 30. In older adults, a normal creatinine can hide reduced GFR.
Up to 92% of a dose appears in urine as inactive metabolites. The label needs no renal dose change but asks for more frequent INR checks.
Half-Life of Drugs: A Worked Example
A drug’s half-life is the time its plasma concentration takes to fall by half. For first-order drugs, about 90% of a dose is gone after 3.3 half-lives and 94% to 97% after 4 to 5 (StatPearls: Elimination Half-Life of Drugs). Because t½ = 0.693 × Vd ÷ clearance, lower clearance from kidney or liver disease means a longer half-life.
Worked example (illustration only): a drug with a 6-hour half-life has 200 mg in the body at noon. That leaves 100 mg at 6 p.m., 50 mg at midnight, 25 mg at 6 a.m., 12.5 mg at noon and 6.25 mg by 6 p.m. the next day, about 3% of the start.
| Half-lives | Drug left | Steady state* |
|---|---|---|
| 0 (0 h) | 100% | 0% |
| 1 (6 h) | 50% | 50% |
| 2 (12 h) | 25% | 75% |
| 3 (18 h) | 12.5% | 87.5% |
| 4 (24 h) | 6.25% | 93.75% |
| 5 (30 h) | 3.125% | 96.9% |
A few drugs, such as ethanol and phenytoin, can follow zero-order elimination, losing a fixed amount per hour once enzymes saturate, so the rule doesn’t apply.
Steady state after 4–5 half-lives
With repeated doses, levels climb until the amount going in equals the amount going out, which takes about 4 to 5 half-lives. A loading dose, based on volume of distribution, gets there sooner (StatPearls). Warfarin’s effective half-life averages about 40 hours, so plasma steady state sits roughly 7 to 8 days (160 to 200 hours) after a dose change, and its label notes the peak anticoagulant effect may lag 72 to 96 hours.
Same drug, different kidneys: digoxin
Digoxin’s label gives a half-life of 1.5 to 2 days with normal kidneys, so steady state takes about 6 to 10 days (4 × 1.5 to 5 × 2). Without urine output the half-life is 3.5 to 5 days, so about 14 to 25 days. The label warns that these patients face high toxicity risk without a dose reduction, and that dialysis doesn’t remove digoxin effectively.
Chapter-matched questions with rationales test whether you can apply half-life and first-pass ideas, not just define them. Browse pharmacology test banks for your edition. They’re self-assessment practice, not your course’s exams. Publishers write them mainly for instructors and some programs restrict them, so check your honor code or ask your instructor; if your program prohibits them, don’t use one.
- Lehne’s Pharmacology for Nursing Care 11th Edition Test Bank — for the 2021 edition; Elsevier’s current one is the 12th (2024).
- Pharmacology: Connections to Nursing Practice 4th Edition Test Bank — for the 4th; Pearson’s current is the 5th (2022).
- Basic and Clinical Pharmacology 14th Edition Test Bank (Katzung) — for the 14th; McGraw Hill now sells the 16th.
Each test bank is matched to one edition and ISBN-13. Check the number on your book before you buy.
Pharmacodynamics: Receptors, Agonists, Antagonists and Therapeutic Index
Pharmacodynamics explains the effect: a drug binds a target, usually a receptor, and activates it (agonist) or blocks it (antagonist). The therapeutic index compares toxic and effective concentrations, showing the safety margin (Merck Manual: Pharmacodynamics).
- Agonist: activates the receptor, as morphine does at opioid receptors.
- Competitive antagonist: occupies the receptor without activating it. Naloxone blocks morphine, and beta-blockers such as atenolol block beta receptors.
- Partial agonist: activates weakly and blunts stronger agonists, like pentazocine (Merck).
Receptors adapt: long-term beta-blockers increase receptor numbers, so abrupt withdrawal can cause tachycardia or severe hypertension, and opioid tolerance partly reflects reduced receptor signaling (StatPearls: Pharmacodynamics). Potency is how much drug you need; efficacy is the biggest effect possible. The two meet in opioid reversal: naloxone’s adult half-life is about 30 to 81 minutes, and its label warns that some opioids outlast it, so keep watching and repeat doses as ordered.
Therapeutic index and narrow-range drugs
The Merck Manual defines the therapeutic index as the minimum toxic concentration divided by the median effective concentration. With a narrow index, small changes in dose, metabolism or kidney function can tip a patient into toxicity, so dosing follows levels or lab results.
| Drug | Monitor | Source says |
|---|---|---|
| Warfarin | INR, bleeding | Narrow range; affected by drugs and vitamin K |
| Digoxin | Level, potassium, kidneys | Toxic levels only slightly above therapeutic |
| Lithium | Level, kidneys, sodium | Toxicity near therapeutic levels |
| Phenytoin | Level | Narrow index; levels guide dosing |
A trough is drawn just before the next dose and a peak after it, so plan administration around the draw times. Our guide to Lehne’s Pharmacology for Nursing Care shows how one textbook organizes prototypes and monitoring.
Pharmacokinetics Across the Lifespan: Nursing Implications
Age and organ function change pharmacokinetics more than almost anything else on a unit. Infants clear many drugs slowly because their liver enzymes and kidneys are immature; older adults often need lower doses as kidney function, liver metabolism and body composition change (Merck Manual: Pharmacokinetics in Older Adults).
| Group | What changes | At the bedside |
|---|---|---|
| Infants | Immature enzymes and kidneys, more body water, less protein binding | Weight-based doses; double-check math |
| Older adults | More fat, less water, lower albumin; less CYP450 activity and first pass | Start low, go slow; use creatinine clearance |
| Kidney disease | Renally cleared drugs accumulate | Check eGFR first; time levels |
| Liver disease | Slower metabolism, lower albumin | Watch for sedation and toxicity |
| Pregnancy | Placental transfer; lithium clearance rises | Check a current drug reference |
Changes stack in older adults. Warfarin’s label reports a greater INR response at 60 and older, and Merck notes some benzodiazepines have half-lives up to 96 hours in older patients, so toxicity can appear days after starting. In neonates, naloxone’s half-life was about 3 hours versus about 1 hour in adults. For weight-based math, practice with our guide to nursing dosage calculations.
- Confirm the route: sublingual dissolves under the tongue; IV and oral doses differ.
- For renally cleared drugs, check the latest creatinine clearance or eGFR.
- Screen new antibiotics, antifungals, herbals and grapefruit for interactions.
- Reassess at the expected peak, and again when a reversal agent may wear off.
Figures here come from FDA labels and references to teach concepts. Follow your program’s textbook, your facility’s policy and your instructor’s reference ranges.
Frequently asked questions
What does ADME stand for?
Absorption, distribution, metabolism and excretion, the four stages of pharmacokinetics. Absorption moves the drug into the blood, distribution carries it to tissues, metabolism changes it chemically, mostly in the liver, and excretion removes it, mostly through the kidneys. Some references also describe liberation, the release of drug from its tablet, as the first step of absorption.
What is the difference between pharmacokinetics and pharmacodynamics?
Pharmacokinetics is what the body does to the drug: absorption, distribution, metabolism and excretion over time. Pharmacodynamics is what the drug does to the body through receptors. Fluconazole raising warfarin exposure is a pharmacokinetic interaction; aspirin adding to warfarin’s bleeding risk is a pharmacodynamic one.
How many half-lives until a drug is eliminated?
About 4 to 5. For a first-order drug, 94% to 97% of a single dose is gone by then, and StatPearls treats it as effectively eliminated. Kidney or liver disease lengthens the half-life, and drugs with zero-order elimination, such as ethanol, don’t follow the rule.
Why do older adults need lower doses?
Kidney function declines, so renally cleared drugs build up even when serum creatinine looks normal. Liver and first-pass metabolism decrease, body fat rises, and lower albumin raises free drug for some medications. Receptor sensitivity can change too. Start low, increase slowly and monitor closely.
What is a narrow therapeutic index drug?
A drug whose toxic concentration sits close to its effective one, so small changes in dose, metabolism or kidney function can cause toxicity or treatment failure. Warfarin, digoxin, lithium and phenytoin are common examples, monitored with blood levels or the INR against your facility’s reference ranges.
Bottom line: build one ADME card tonight
Pick one drug from this week’s unit and write five lines: route and bioavailability, protein binding, metabolism, excretion with half-life, and what you monitor. Then explain it aloud the way the warfarin callouts do. For chapter-matched questions to check it, browse our nursing test banks for your edition.
Sources & further reading
- StatPearls (NCBI Bookshelf) — Pharmacokinetics
- StatPearls (NCBI Bookshelf) — Elimination Half-Life of Drugs
- StatPearls (NCBI Bookshelf) — First-Pass Effect
- Open RN Nursing Pharmacology, 2nd ed. (NCBI Bookshelf) — Chapter 1
- Merck Manual Professional — Pharmacokinetics in Older Adults
- DailyMed (NLM) — Warfarin sodium tablets label
- DailyMed (NLM) — Lanoxin (digoxin) tablets label
