From the Guidelines
Renal clearance is the key pharmacokinetic property influencing gabapentin and pregabalin dosing differences in patients with impaired renal function.
Key Considerations
- Both gabapentin and pregabalin require dosage reduction in patients with renal insufficiency, with adjustments made in relation to creatinine clearance 1.
- Gabapentin has nonlinear pharmacokinetics due to saturable absorption, requiring careful titration, whereas pregabalin has linear pharmacokinetics, making dosing more straightforward 1.
- The dosing of gabapentin and pregabalin should be adjusted based on renal function to avoid dose-dependent adverse effects, such as dizziness and sedation 1.
Dosing Recommendations
- Gabapentin: initiate at low dosages (100-300 mg at bedtime or 100-300 mg 3 times daily) and titrate cautiously, reducing the dose if impaired renal function is present 1.
- Pregabalin: initiate at 50 mg 3 times daily or 75 mg twice daily, and titrate up to 300 mg/d after 3-7 days, then by 150 mg/d every 3-7 days as tolerated, reducing the dose if impaired renal function is present 1.
From the FDA Drug Label
Pregabalin clearance is nearly proportional to creatinine clearance (CLcr). Apparent oral clearance of gabapentin was directly proportional to creatinine clearance.
The key pharmacokinetic property influencing gabapentin and pregabalin dosing differences in patients with impaired renal function is renal clearance, which is directly proportional to creatinine clearance (CLcr) 2 3. This means that as renal function declines, the clearance of both gabapentin and pregabalin decreases, leading to increased drug concentrations and potential toxicity. Therefore, dose adjustment is necessary in patients with renal impairment to avoid adverse effects.
From the Research
Pharmacokinetic Properties of Gabapentin and Pregabalin
The key pharmacokinetic property influencing gabapentin and pregabalin dosing differences in patients with impaired renal function is their renal elimination. Both drugs are excreted renally, with elimination half-lives of approximately 6 hours for pregabalin 4 and 5 to 9 hours for gabapentin 5.
Factors Affecting Dosing
- The absolute bioavailability of gabapentin drops from 60% to 33% as the dosage increases from 900 to 3600 mg/day, while the absolute bioavailability of pregabalin remains at > or = 90% irrespective of the dosage 6.
- Gabapentin exhibits saturable absorption, making its pharmacokinetics less predictable, whereas pregabalin absorption is linear (first order), with plasma concentrations increasing proportionately with increasing dose 6.
- Pregabalin plasma clearance is essentially equivalent to renal clearance, indicating that pregabalin undergoes negligible nonrenal elimination 4.
- Gabapentin plasma clearance is linearly related to creatinine clearance, and dosage is readily adjusted based on renal function 5.
Implications for Patients with Impaired Renal Function
- The dosing of both gabapentin and pregabalin needs to be adjusted in patients with impaired renal function due to their renal elimination 4, 5.
- The pharmacokinetic advantages of pregabalin, such as its linear absorption and higher bioavailability, may translate into an improved pharmacodynamic effect in patients with impaired renal function 6.