Abstracts

To compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties of pregabalin (PGB) and gabapentin (GBP). The similarities and differences between the PK and PD properties of PGB and GBP were assessed using clinical pharmacology and efficacy studies. Significant PK and PD differences between PGB and GBP were found. PGB is absorbed rapidly (peak concentrations [le]1hr) yielding plasma concentrations that increase linearly with increasing dose. In contrast, GBP is absorbed slowly (peak concentrations [sim]3-4hr) yielding plasma concentrations that do not increase proportionally with dose. Intersubject variability in drug exposure is generally lower for PGB than GBP. PGB oral bioavailability is [ge]90% irrespective of clinical dose whereas GBP bioavailability drops from 60% to 33% as dose increases from 900 to 3600mg/day. The amount of PGB and GBP absorbed is unaffected by food. Neither PGB nor GBP are metabolized in humans, inhibit the enzymes responsible for the metabolism of other drugs, nor bind to plasma proteins. Both drugs are eliminated renally (t[sub]1/2[/sub] [sim]6hr). Increasing doses of GBP are associated with decreasing seizure frequency in 90% of patients. In these patients, the decrease in seizures reaches a 25% reduction in seizures from baseline at doses of 900 mg/day, with little further increase in response with higher doses. In contrast, increasing doses of PGB are associated with decreasing seizure frequency in 75% of patients. In these patients, the decrease in seizure frequency reaches a maximum 100% reduction in seizures from baseline. A dose of PGB [sim]186 mg/day is expected to decrease the seizure frequency by 50% of baseline. PGB can be administered twice- or three-times daily while GBP is administered three-times daily. Pregabalin, a second generation [sub]^[alpha][/sub][sub]2[/sub]-[delta] ligand, was found to have distinct PK and PD advantages over gabapentin. (Supported by Pfizer Inc.)