| Sumario: | What is known and Objective: ABT-594 is a non-opioid, non-NSAID analgesic. The objective of this work was to characterize the population pharmacokinetics of ABT-594 in subjects with neuropathic pain. Methods: Efficacy, safety and pharmacokinetics of ABT-594 in subjects with painful diabetic polyneuropathy were evaluated in a randomized, double-blind, placebo-controlled, parallel-group, multi-centre, 7-week Phase 2 study. Subjects ( N = 266) were approximately equally divided into four groups to receive BID regimens of placebo or 150, 225 and 300 μg of ABT-594. ABT-594 concentrations were determined from all subjects, whereas a subset of subjects provided intensive pharmacokinetic samples on two occasions. One- and two-compartment models were explored for characterizing plasma ABT-594 concentration-time profiles. The relative importance of covariates (age, weight, body surface area, creatinine clearance, gender, nicotine use and albumin concentrations) was examined by use of the likelihood ratio test. Model building was accomplished using stepwise forward selection ( P < 0·05) and backward elimination ( P < 0·005) of covariates. Population analyses were performed using NONMEM. Results and Discussion: Optimal characterization of the plasma concentration data was achieved using a one-compartment base model. Creatinine clearance and age were found to be significant covariates in the forward selection process; backward elimination process identified only creatinine clearance as a significant covariate. What is new and Conclusion: A population pharmacokinetic model was developed to characterize ABT-594 concentrations in subjects with neuropathic pain. As ABT-594 is primarily eliminated as unchanged drug in the urine, creatinine clearance and age were significant covariates of clearance with creatinine clearance being the optimal predictor of ABT-594 clearance.
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