Ana Carolina Costa

and 7 more

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.