Is gabapentin (Gabapentin) excreted by the kidneys in a patient with impaired renal function (negligible creatinine clearance) but near normal urine output?

Gabapentin Excretion in Patients with Negligible Creatinine Clearance but Normal Urine Output

Yes, gabapentin is primarily excreted by the kidneys, with 85% of the dose excreted unchanged in the urine through glomerular filtration and tubular secretion, even in patients with negligible creatinine clearance but normal urine output. 1

Pharmacokinetics of Gabapentin in Renal Impairment

• Gabapentin is almost exclusively eliminated by renal excretion as unchanged drug, with 85% of the dose excreted by renal clearance 1
• Gabapentin is not appreciably metabolized in humans, meaning kidney function is the primary determinant of drug clearance 1
• Renal clearance of gabapentin is directly proportional to creatinine clearance, making dosage adjustment necessary in patients with impaired renal function 1
• In patients with severe renal impairment (creatinine clearance <30 mL/min), the elimination half-life of gabapentin increases from approximately 6.5 hours (normal renal function) to 52 hours 1
• Mean plasma clearance (CL/F) decreases from approximately 190 mL/min in normal renal function to 20 mL/min in severe renal impairment 1

Gabapentin in Anuric Patients and Dialysis

• In anuric patients, the elimination half-life of gabapentin is dramatically prolonged to approximately 132 hours (5.5 days) 1, 2
• Hemodialysis significantly reduces the elimination half-life to approximately 3.8 hours during the procedure, indicating that dialysis has a substantial effect on gabapentin elimination 1
• Peritoneal dialysis can also remove gabapentin, though less efficiently than hemodialysis, with an estimated elimination half-life of 41.33 hours during continuous peritoneal dialysis 3
• Approximately 35% of a gabapentin dose can be recovered in dialysate during hemodialysis, with a mean hemodialysis clearance of 142 mL/min (approximately 93% of dialyzer creatinine clearance) 2

Clinical Implications and Dosing Considerations

• In patients with negligible creatinine clearance but preserved urine output, gabapentin will still be excreted in the urine, but at a significantly reduced rate 1
• The FDA label specifically states that dosage adjustment is necessary in adult patients with compromised renal function 1
• The presence of normal urine output despite negligible creatinine clearance suggests that some filtration is occurring, but the drug will accumulate significantly due to reduced clearance 1
• After hemodialysis, gabapentin plasma concentrations can increase by approximately 30% during the first 2 hours due to drug redistribution in the body 2

Monitoring and Safety Considerations

• Patients with renal impairment are at higher risk for gabapentin toxicity, which can manifest as neurological symptoms including altered mental status, dizziness, and myoclonus 4, 5
• Drug monitoring may be beneficial in patients with severe renal impairment to avoid unintended overdose, as symptoms of toxicity can prompt extensive diagnostic workups when the underlying cause is supratherapeutic drug levels 4
• Elderly patients with decreased renal function are particularly susceptible to gabapentin toxicity due to age-related decreases in renal function 1
• In patients with end-stage renal disease, continuous renal replacement therapies like CVVHD have been successfully used to treat gabapentin toxicity 5

In conclusion, while urine output may be preserved in a patient with negligible creatinine clearance, the ability to clear gabapentin will still be severely compromised. Careful dosage adjustment and monitoring are essential to prevent toxicity in such patients.