A phase I, single-dose study of the disposition of14C- radiolabeled gabapentin enacarbil in healthy male volunteers

International Journal of Clinical Pharmacology and Therapeutics

Volumn 49, Issue 2, 2011, Pages 109-115

  Lal, R ^a   Sukbuntherng, J ^a   Ho, J ^a   Cundy, K C ^a  

^a XenoPort Inc   (United States)

Author keywords

Gabapentin enacarbil; GSK1838262; Pharmacokinetics; XP13512

Indexed keywords

CARBON 14; GABAPENTIN; GABAPENTIN ENACARBIL;

ABNORMAL SENSATION; ADULT; ANOREXIA; AREA UNDER THE CURVE; ARTICLE; CONSTIPATION; DIZZINESS; DRUG ABSORPTION; DRUG DISPOSITION; DRUG ELIMINATION; DRUG FECES LEVEL; DRUG METABOLISM; DRUG STRUCTURE; DRUG URINE LEVEL; DYSPEPSIA; HUMAN; HUMAN EXPERIMENT; ISOTOPE LABELING; KIDNEY CLEARANCE; LABORATORY TEST; MALE; MAXIMUM PLASMA CONCENTRATION; MUSCLE TIGHTNESS; NIGHTMARE; NORMAL HUMAN; OPEN STUDY; PHASE 1 CLINICAL TRIAL; RADIOACTIVITY; SIDE EFFECT; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; VITAL SIGN;

ADOLESCENT; ADULT; AREA UNDER CURVE; CARBAMATES; CARBON RADIOISOTOPES; GAMMA-AMINOBUTYRIC ACID; HUMANS; MALE; MIDDLE AGED;

EID: 78751680483     PISSN: 09461965     EISSN: None     Source Type: Journal    
DOI: 10.5414/CPP49109     Document Type: Article

References (16)

1. Stewart BH, Kugler AR, Thompson PR, Bock-brader HN. A saturable transport mechanismin the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma. Pharm Res. 1993; 10: 276-281.
2. Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, Anders MW, Endou H. Transport of amino acid-related compounds mediated by L-Type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Mol Pharmacol. 2002; 61: 729-737. (Pubitemid 34273151)
3. Cundy KC, Branch R, Chernov-Rogan T, Dias T, Estrada T, Hold K, Koller K, Liu X, Mann A, Panuwat M, Raillard SP, Upadhyay S, Wu QQ, Xiang JN, Yan H, Zerangue N, Zhou CX, Barrett RW, Gallop MA. XP13512 [(±)-1-([(alpha- isobutanoyloxyethoxy) carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: I. Design, synthesis, enzymatic conversion to gabapentin, and transport by intestinal solute transporters. J Pharmacol Exp Ther. 2004; 311: 315-323.
4. Cundy KC, Annamalai T, Bu L, De Vera J, Estrela J, Luo W, Shirsat P, Torneros A, Yao F, Zou J, Barrett RW, Gallop MA. XP13512 [(±)-1- ([(alphaisobutanoyloxyethoxy) carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: II. Improved oral bioavailability, dose proportionality, and colonic absorption compared with gabapentin in rats and monkeys. J Pharmacol Exp Ther. 2004; 311: 324-333.
5. Tai E, Tate E, Sukbuntherng J, Lal R, Cundy KC. Human carboxylesterase-2 is the primary enzyme responsible for the hydrolysis of XP13512/GSK1838262. AAPS Journal. 2008; 10: 2.
6. Cundy KC, Sastry S, Luo W, Zou J, Moors TL, Canafax DM. Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin. J Clin Pharmacol. 2008; 48: 1378-1388.
7. Lal R, Sukbuntherng J, Luo W, Chen D, Vu A, Tovera J, Cundy KC. Pharmacokinetics and tolerability of single escalating doses of gabapentin enacarbil: a randomized-sequence, double-blind, placebo-controlled, crossover study in healthy volunteers. Clin Ther. 2009; 31: 1776-1786.
8. Radulovic LL, Turck D, von Hodenberg A, Vollmer KO, McNally WP, DeHart PD, Hanson BJ, Bock-brader HN, Chang T. Disposition of gabapentin (neurontin) in mice, rats, dogs, and monkeys. Drug Metab Dispos. 1995; 23: 441-448.
9. World Medical Association. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects: 2004 Revision.
10. Kushida CA, Becker PM, Ellenbogen AL, Canafax DM, Barrett RW, the XP052 Study Group. Randomized, double-blind, placebo-controlled trial of XP13512/GSK1838262 in patients with RLS. Neurology 2009; 72: 439-446.
11. ICRP Publication 30. Limits for the intake of radionuclides by workers. Part 1. Annals of the ICRP: 1979; 2: 3-4.
12. US Food and Drug Administration. Code of Federal Regulations 21, vol. 5; 2009 revision.
13. Dain JG, Collins JM, Robinson WT. A regulatory and industrial perspective of the use of carbon-14 and tritium isotopes in human ADME studies. Pharm Res. 1994; 11: 925-928.
14. Quimby E, Feitelberg S. Radioactive Isotopes in Medicine and Biology. Philadelphia: Lea and Feitelberg; 1963.
15. Shelein B. The Health Physics and Radiological Health Handbook. Silver Spring, Maryland: Scinta, Inc.; 1992.
16. Vollmer KO, von Hodenberg A, Kolle EU. Pharmacokinetics and metabolism of gabapentin in rat, dog and man. Arzneimittelforschung 1986; 36: 830-839.