Population pharmacokinetics of gabapentin in patients with neuropathic
pain: the role of glycaemic control
Abstract
Aims: Gabapentin (GBP) is an α2-δ ligand drug widely used to treat
neuropathic pain, especially diabetic neuropathy. The drug presents a
saturable absorption in therapeutic doses and it is mainly eliminated
unchanged in the urine. GBP excretion has been suggested to be dependent
on glomerular filtration rate and active transport by renal drug
carriers. Our objective was to evaluate the role of diabetes and
glycaemic control on GBP pharmacokinetics using a population
pharmacokinetic modelling approach. Methods: A clinical trial was
conducted in participants with neuropathic pain of intensity ≥ 4
evaluated by visual analogue scale (VAS) (n=29), due to lumbar or
cervical disc herniation or due to diabetic neuropathy. All participants
were treated with a single oral dose of 300 mg GBP. Blood samples were
collected up to 24 hours after GBP administration. A population
pharmacokinetic analysis was conducted to evaluate the inter-individual
variability considering as potential covariates weight, height, body
mass index (BMI), sex, biomarkers of renal function and diabetes, and
genotypes for the main genetic polymorphisms of SLC22A2 and SLC22A4, the
genes encoding the transporters for organic cations OCT2 and OCTN1.
Results: Population estimates for lag time, first-order absorption rate,
total clearance and apparent volume of distribution at steady state were
0.32 h, 1.13 h-1, 14.7 L/h and 140 L, respectively. The total plasma
clearance of GBP is affected by the estimated glomerular filtration rate
and the volume of distribution increases with higher glycaemic levels.
Conclusion: GBP population pharmacokinetics was affected by renal
function and glycaemic control.