A phase I, single-dose study of the disposition of 14C-radiolabeled gabapentin enacarbil in healthy male volunteers.

UNLABELLED: Gabapentin enacarbil (GEn) is a prodrug of gabapentin that is effective in restless legs syndrome (RLS) and has dose-proportional gabapentin exposure. OBJECTIVE: This Phase I, open-label, non-randomized, single-center study of 14C-GEn in healthy male volunteers (XenoPort, Inc. protocol: XP065) characterized the mass balance, absorption, metabolism, and elimination pathways of GEn after oral administration of 14C-GEn. METHODS: Subjects received GEn 600 mg as two gelatin capsules containing 300 mg immediate release GEn solution each with approximately 50 µCi of 14C-GEn. Pharmacokinetic assessments included total radioactivity excreted in urine (Aeu(0-t)) and feces (Aef(0-t)), mean maximum concentration (Cmax), 14C-GEn-derived radioactivity in plasma and whole blood, and gabapentin area under the concentration-time curve extrapolated to infinity (AUC0-inf). Tolerability was assessed using adverse events (AEs), vital signs, clinical laboratory tests, and ECGs. Six male subjects aged 24 - 46 years were recruited to the study. RESULTS: Mean total recovery of 14C-GEn-derived radioactivity was 99.3% (94.1% in urine and 5.2% in feces). Mean Cmax and AUC for GEn-derived total radioactivity were similar in whole blood and plasma; the blood to plasma ratio for 14C-GEn-derived total radioactivity was 0.91. 14C-gabapentin was the only radioactive species present in blood. More than 85% of the radioactive dose was recovered in urine within 24 h of dosing. Eight treatment-emergent AEs were reported by 3 subjects; all were mild in intensity. There were no clinically relevant changes in vital signs, laboratory values, or ECGs. CONCLUSIONS: GEn was extensively absorbed and rapidly eliminated from plasma and whole blood.