Gabapentin to pregabalin therapy transition: A pharmacokinetic simulation

摘要

The objective of this modeling study was to assess different dosage regimens that might be used to guide clinicians in transitioning patients from gabapentin to pregabalin therapy when such a transition is clinically warranted. Two different gabapentin to pregabalin transition designs were simulated based on their respective population pharmacokinetic profiles. The first design involved immediate discontinuation of gabapentin therapy with initiation of pregabalin therapy at the next scheduled dose period. The second design featured a gradual transition involving coadministration of 50% of the gabapentin dosage and 50% of the desired pregabalin dosage for 4 days, followed by discontinuation of gabapentin and fully targeted dosages of pregabalin. Both transition designs were studied at 3 dosage levels: gabapentin 900 mg/d to pregabalin 150 mg/d, gabapentin 1800 mg/d to pregabalin 300 mg/d, and gabapentin 3600 mg/d to pregabalin 600 mg/d. Overall drug exposure achieved during the 2 transition designs was the sum of the gabapentin and pregabalin concentrations, expressed as pregabalin-equivalent concentrations. The pharmacokinetic simulations show that during the transition period in both designs, predicted pregabalin-equivalent concentrations did not depart from those calculated during periods of steady-state gabapentin or pregabalin monotherapy. Transition from gabapentin to pregabalin was seamless and rapid, with predicted pregabalin-equivalent concentrations highly comparable with plasma pregabalin concentrations within 1 day of pregabalin initiation in the immediate discontinuation model and within 1 day of gabapentin cessation in the gradual discontinuation model. These data suggest that transitioning patients from gabapentin to pregabalin could theoretically be achieved by either of the 2 approaches assessed.