Excretion — Pharmacokinetics

Key Points

• Excretion is the fourth and final ADME stage: the body eliminates remaining parent drugs and metabolites from systemic circulation.
• The kidney is the primary route — glomerular filtration, tubular secretion, and partial tubular reabsorption determine how efficiently drugs are eliminated in urine.
• Kidney function is measured by serum creatinine, GFR, and creatinine clearance; impaired renal function requires dose adjustment.
• The liver excretes drug metabolites into bile → intestine → feces; some drugs undergo enterohepatic recirculation (reabsorbed from the intestine).
• Other routes include the lungs (alcohol, anesthetic gases), breast milk, sweat, and reproductive fluids.
• Breast milk can contain drugs and metabolites — always consult a drug reference before administering medications to breastfeeding patients.
• Life span: neonates have immature kidneys (↓GFR → ↓excretion → higher drug levels); older adults experience declining renal and hepatic function → “Start low and go slow.”

Pathophysiology

Excretion is the final stage of pharmacokinetics (ADME). After a drug has been absorbed, distributed, and metabolized, the body must eliminate the remaining parent drug molecules and metabolites. The primary organ of excretion is the kidney; secondary routes include the liver (via bile), lungs, and minor routes (sweat, tears, breast milk, reproductive fluids).

Classification

Renal Excretion (Primary Route)

The kidneys filter blood through three sequential processes:

1. Glomerular filtration: Unbound drug and small metabolites pass from blood into the filtrate.
2. Tubular secretion: Active transport systems in the renal tubule secrete additional drug molecules from blood into the filtrate.
3. Tubular reabsorption: A portion of filtered drug is reabsorbed back into the bloodstream; only the fraction not reabsorbed is excreted in urine.

The net rate of renal drug excretion depends on the balance of these three processes. Known sex differences exist: renal clearance (glomerular filtration, tubular secretion, tubular reabsorption) is generally higher in biological males than females, affecting the pharmacokinetics of renally eliminated drugs.

Factors that reduce renal excretion:

• Chronic kidney disease (CKD): Progressive reduction in GFR → slowed drug elimination → drug accumulation → dose reduction or extended dosing intervals required.
• Aging: GFR naturally declines with age → less efficient drug excretion even without overt renal disease.
• Heart failure: Decreased cardiac output → reduced renal perfusion → impaired glomerular filtration → drug accumulation.
• Other conditions reducing renal blood flow: Shock, hypovolemia, hypotension — all impair renal perfusion and drug elimination, requiring dosing adjustments.

Renal function lab assessments: Serum creatinine, glomerular filtration rate (GFR), creatinine clearance — used to estimate excretion capacity and guide dose adjustment.

Hepatic (Biliary) Excretion

The liver excretes drugs and metabolites into bile via active transport by hepatocytes:

• Bile travels through bile ducts → gallbladder → small intestine.
• In the intestine, some drugs are partially reabsorbed back into the bloodstream (enterohepatic recirculation), prolonging drug action.
• Other drugs are metabolized by intestinal bacteria and then reabsorbed.
• Unabsorbed drugs, byproducts, and metabolites are excreted in feces.

Factors reducing hepatic excretion: Liver disease (cirrhosis, hepatitis) impairs hepatocyte function → reduced biliary excretion → dose adjustment needed. Conditions reducing hepatic blood flow (shock, hypovolemia, hypotension) also impair hepatic excretion.

Liver function assessment: Alanine transaminase (ALT) and aspartate aminotransferase (AST) — elevated levels indicate hepatic damage and signal reduced excretory capacity.

Pulmonary Excretion

Some volatile drugs are eliminated via the lungs:

• Examples: Ethanol (alcohol), anesthetic gases (e.g., isoflurane, desflurane).
• Excretion occurs through exhalation; rate depends on pulmonary blood flow and drug volatility.

Other Routes

Drugs and metabolites can also be excreted in:

• Sweat and tears — minor routes, generally clinically insignificant except for contact (e.g., drug residue on skin).
• Breast milk — clinically significant; nursing infants can be exposed to drugs or toxic metabolites ingested by the mother. Nurses must consult a current, evidence-based drug reference (e.g., LactMed) before administering any medication to a breastfeeding patient and must notify the prescriber of potential concerns.
• Reproductive fluids (seminal fluid) — potential for partner exposure to drug molecules.

Nursing Assessment

NCLEX Focus

Know the primary route of drug excretion (kidneys), which lab values assess renal function (GFR, creatinine clearance, serum creatinine), and why dose adjustment is required in renal and hepatic impairment. Understand the breast milk safety obligation and the “Start low and go slow” principle for older adults.

• Assess renal function before administering renally excreted drugs: serum creatinine, BUN, GFR, creatinine clearance.
• Assess hepatic function for drugs excreted via bile: ALT, AST, clinical signs of liver disease (jaundice, ascites, confusion).
• Assess cardiovascular status — heart failure or shock reduces renal and hepatic perfusion and impairs drug elimination.
• Assess breastfeeding status before administering any medication; consult LactMed or equivalent reference.
• Assess age-related changes in renal and hepatic function — older adults require particular vigilance even with normal laboratory values (age-related functional decline may not be fully captured by standard labs).
• Assess pediatric patients’ weight in kilograms for weight-based dosing; assess for early signs of drug toxicity given immature renal excretion.

Nursing Interventions

• Obtain and trend renal function labs (GFR, creatinine clearance, serum creatinine) for all patients on renally excreted drugs; collaborate with pharmacist for dose adjustment when values fall below normal thresholds.
• Obtain hepatic function labs (ALT, AST, bilirubin) and assess for clinical hepatic impairment; adjust dosing in consultation with the prescriber and pharmacist.
• Monitor urine output as a proxy for renal perfusion and excretory capacity — oliguria suggests impaired drug elimination.
• Consult a current drug reference before administering medications to breastfeeding mothers; document discussion with prescriber if any concern is identified.
• Verify weight-based pediatric dosing calculations independently before administration; monitor infants and children closely for adverse effects and toxicity.
• Apply the principle of “Start low and go slow” for older adults receiving renally or hepatically excreted drugs — anticipate lower therapeutic doses and longer dosing intervals.

Renal Impairment and Drug Accumulation

Patients with CKD or acute kidney injury may accumulate renally excreted drugs rapidly, even at standard doses. This is particularly dangerous for drugs with narrow therapeutic indices (e.g., digoxin, aminoglycoside antibiotics, lithium). Always verify GFR and creatinine clearance before initiating therapy and establish a monitoring plan with the prescriber and pharmacist.

Life Span Considerations

Neonate and Pediatric

• Immature kidneys have decreased glomerular filtration, tubular reabsorption, and tubular secretion at birth → neonates do not excrete medications efficiently.
• Dosing is typically weight-based (per kilogram) with smaller total doses to account for reduced excretory capacity.
• Higher levels of free circulating drug are expected in neonates/infants → toxicity can develop rapidly.
• Nurses must recheck all weight-based doses before administration and monitor closely for early signs of adverse effects and toxicity.
• Kidney function matures progressively through the first year of life.

Older Adult

• Kidney and liver function decline with aging → both renal and biliary excretion are reduced.
• Drug half-life is prolonged → greater risk for drug accumulation and toxicity at standard adult doses.
• Guiding principle: “Start low and go slow” — initiate at lower doses, titrate cautiously, and use extended dosing intervals.
• Some medications may be contraindicated in older adults due to insufficient excretory capacity (see Beers Criteria for Potentially Inappropriate Medications in Older Adults).

Pharmacology

Excretion Factor	Mechanism	Clinical Example	Nursing Implication
Renal impairment (CKD)	↓GFR → ↓drug filtration → accumulation	Digoxin in CKD → toxicity at standard dose	Monitor GFR/creatinine clearance; dose-adjust with pharmacist
Heart failure	↓Cardiac output → ↓renal perfusion → ↓drug elimination	Loop diuretic accumulation in advanced heart failure	Monitor urine output and renal labs; assess hemodynamic status
Hepatic impairment	↓Hepatocyte function → ↓biliary excretion → drug accumulation	Morphine accumulation in cirrhosis → respiratory depression	Check ALT/AST; collaborate on dose reduction; monitor sedation
Enterohepatic recirculation	Intestinal reabsorption → prolonged drug action	Some oral contraceptives recirculate → prolonged effect, interaction risk	Educate on drug-drug interactions affecting the enterohepatic cycle
Pulmonary excretion	Volatile drugs exhaled via lungs	Ethanol on breath; anesthetic gas elimination post-surgery	Assess respiratory function; no direct dose intervention needed
Breast milk excretion	Lipid-soluble/ionizable drugs concentrate in breast milk	Codeine metabolite (morphine) → neonatal respiratory depression in nursing	Consult LactMed/drug reference; notify prescriber; consider alternatives
Neonatal immature kidneys	↓GFR → ↓excretion → ↑free drug	Gentamicin in neonates → toxicity at adult mg/kg dose	Use weight-based dosing; recheck calculations; monitor drug levels
Older adult ↓renal function	Age-related GFR decline → prolonged drug half-life	Metformin in older adults with renal decline → lactic acidosis risk	”Start low and go slow”; monitor renal function regularly

Clinical Judgment Application

Clinical Scenario

A 68-year-old patient with chronic kidney disease (GFR 28 mL/min/1.73 m²) is admitted for a urinary tract infection and prescribed a standard adult dose of an aminoglycoside antibiotic. After three days, the patient reports ringing in the ears and diminished hearing.

• Recognize Cues: Tinnitus and hearing loss (signs of aminoglycoside ototoxicity) in a patient with CKD on a standard adult aminoglycoside dose.
• Analyze Cues: Aminoglycosides are renally excreted. GFR 28 mL/min indicates significantly reduced excretory capacity → standard dose leads to drug accumulation → plasma levels exceed toxic threshold → ototoxicity.
• Prioritize Hypotheses: Aminoglycoside toxicity (ototoxicity) due to impaired renal excretion is the priority concern; nephrotoxicity may also be occurring concurrently.
• Generate Solutions: Hold next aminoglycoside dose; notify prescriber immediately; obtain serum drug trough level and GFR; assess renal function trends; evaluate alternative antibiotics with renal dose adjustment protocols.
• Take Action: Withhold dose, document audiological findings and renal labs, notify provider stat, consult pharmacist for individualized dosing based on creatinine clearance.
• Evaluate Outcomes: Prescriber extends dosing interval based on pharmacokinetic calculation; audiological follow-up scheduled; patient educated on symptoms requiring immediate reporting.

Related Concepts

• pharmacokinetics-and-pharmacodynamics — Excretion is the fourth and final ADME stage.
• metabolism-pharmacokinetics — Hepatic metabolism precedes biliary excretion; both processes are impaired by liver disease.
• distribution-pharmacokinetics — Drug-protein binding affects the free fraction available for glomerular filtration.
• loop-diuretics — Furosemide is both renally excreted and acts on the kidneys; renal impairment affects its elimination and response.
• anticoagulants — Some anticoagulants (e.g., dabigatran) are primarily renally excreted; CKD dramatically increases bleeding risk.

Self-Check

1. What three renal processes govern how much of a drug is excreted in urine? How do they interact?
2. A patient with a GFR of 25 mL/min is prescribed digoxin at the standard adult dose. What excretion-related concern does the nurse have, and what action should be taken?
3. A breastfeeding mother is prescribed a new pain medication. What is the nurse’s obligation before administering the drug, and why?