How is ciprofloxacin (Cipro) excreted in patients with impaired renal function?

Ciprofloxacin Excretion

Ciprofloxacin is eliminated primarily through renal excretion (40-50% as unchanged drug in urine), with significant additional clearance through hepatic metabolism and biliary/transintestinal elimination. 1

Primary Excretion Pathways

Renal Excretion (Predominant Route)

• Approximately 40-50% of an oral dose is excreted unchanged in the urine 1
• The renal clearance of ciprofloxacin is approximately 300 mL/minute, which substantially exceeds the normal glomerular filtration rate of 120 mL/minute 1
• Active tubular secretion plays a significant role in renal elimination, as evidenced by renal clearance exceeding glomerular filtration 1, 2
• Urinary excretion is virtually complete within 24 hours after dosing 1
• After a 250 mg oral dose, urine concentrations typically exceed 200 μg/mL during the first two hours and remain approximately 30 μg/mL at 8-12 hours post-dose 1
• In healthy volunteers, renal clearance accounts for 66.6% of total serum clearance, with net tubular secretion contributing substantially 2

Non-Renal Clearance Pathways

• Approximately 20-35% of an oral dose is recovered in feces within 5 days, arising from biliary clearance or transintestinal elimination 1
• Hepatic metabolism accounts for approximately 15% of the dose, producing four metabolites with varying antimicrobial activity 1
• Bile concentrations are several-fold higher than serum concentrations, though only a small amount (1-2%) is recovered as unchanged drug or metabolites 1

Excretion in Renal Impairment

Dosing Adjustments Required

• For creatinine clearance 30-50 mL/min: reduce to 250-500 mg every 12 hours 1
• For creatinine clearance 5-29 mL/min: reduce to 250-500 mg every 18 hours 1
• For hemodialysis or peritoneal dialysis patients: 250-500 mg every 24 hours (administered after dialysis) 1
• In anephric patients, serum clearance is approximately 50% of normal subjects, necessitating maximal dose reduction of 50% when creatinine clearance falls to 20-30 mL/min/1.73 m² 2

Pharmacokinetic Changes in Renal Dysfunction

• The elimination half-life is only slightly prolonged (~20%) in renal impairment, increasing from approximately 4 hours to 4-5 hours 1, 2
• Plasma clearance correlates with creatinine clearance, while non-renal clearance remains independent of renal function 3
• Alternative pathways of elimination (hepatic metabolism and biliary/intestinal clearance) partially compensate for reduced renal excretion 1
• Renal clearance of ciprofloxacin correlates strongly with creatinine clearance (rs = 0.93, P < 0.001) 3

Clinical Considerations

Drug Interactions Affecting Excretion

• Co-administration of probenecid reduces ciprofloxacin renal clearance by approximately 50% and increases systemic circulation concentrations by 50% 1, 2
• This interaction confirms that active tubular secretion is a major component of renal elimination 2

Monitoring in Renal Impairment

• Patients with severe infections and severe renal impairment may receive 750 mg at adjusted intervals, but require careful monitoring 1
• The reduced dose should be administered every 12 hours despite variability in terminal half-life in renal impairment 2

Dialysis Considerations

• Ciprofloxacin is not significantly removed by hemodialysis due to high molecular weight, wide tissue distribution, high protein binding (20-40%), and rapid hepatic metabolism 4, 1
• Supplemental dosing after hemodialysis is not necessary 4
• Administering the drug after dialysis facilitates directly observed therapy and prevents premature drug removal 4