PMID- 21255527
OWN - NLM
STAT- MEDLINE
DCOM- 20110324
LR  - 20221222
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 49
IP  - 2
DP  - 2011 Feb
TI  - A phase I, single-dose study of the disposition of 14C-radiolabeled gabapentin 
      enacarbil in healthy male volunteers.
PG  - 109-15
AB  - 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 microCi 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.
FAU - Lal, R
AU  - Lal R
AD  - XenoPort, Inc., Santa Clara, CA, USA. ritu.lal@xenoport.com
FAU - Sukbuntherng, J
AU  - Sukbuntherng J
FAU - Ho, J
AU  - Ho J
FAU - Cundy, K C
AU  - Cundy KC
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic 
      acid)
RN  - 0 (Carbamates)
RN  - 0 (Carbon Radioisotopes)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Carbamates/adverse effects/*pharmacokinetics
MH  - *Carbon Radioisotopes
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - gamma-Aminobutyric Acid/adverse effects/*analogs & derivatives/pharmacokinetics
EDAT- 2011/01/25 06:00
MHDA- 2011/03/25 06:00
CRDT- 2011/01/25 06:00
PHST- 2011/01/25 06:00 [entrez]
PHST- 2011/01/25 06:00 [pubmed]
PHST- 2011/03/25 06:00 [medline]
AID - 8339 [pii]
AID - 10.5414/cpp49109 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2011 Feb;49(2):109-15. doi: 10.5414/cpp49109.