Residual neuromuscular blockade (RNB) commonly occurs when using neuromuscular blockers and increases the risk for pulmonary complications, such as airway obstruction and severe hypoxemia, in extubated patients. Rocuronium exhibits a high variability in recovery time, contributing to an increased risk for RNB. This study aimed to identify and characterize the sources of variability in rocuronium exposure and response via a population pharmacokinetic/pharmacodynamic (PK/PD) analysis and to apply the developed PK/PD model to investigate clinical implications. A nonlinear mixed-effect model was developed for rocuronium in patients undergoing general anaesthesia, using doses of 0.3–1.2 mg/kg. Plasma concentrations and the neuromuscular block [train of four ratio] were assessed up to 6 h after dosing. The influence of age, body mass index, renal function, and sex on PK and PD was explored. Simulations were performed to predict the recovery time. A two-compartment model with linear elimination and an indirect sigmoid I-max model was used to describe PK and PD. The transfer rate into the periphery increases with age. The predicted recovery time was significantly longer in older subjects compared to young adults following single bolus administrations of doses ≥ 0.7 mg/kg. Our findings suggest that geriatric patients take slightly longer to recover than younger adults due to an age-dependent increase in tissue uptake. However, a priori dose adjustments for rocuronium in elderly patients are not feasible, since age contribution is overshadowed by the overall variability in the recovery time.

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.