Population pharmacokinetics and pharmacodynamics of gabapentin after administration of gabapentin enacarbil

Journal of Clinical Pharmacology

Volumn 53, Issue 1, 2013, Pages 29-40

  Lal, Ritu ^a   Sukbuntherng, Juthamas ^b   Luo, Wendy ^a   Tovera, James ^a   Lassauzet, Marie Liesse ^a   Cundy, Kenneth C ^a  

^a XenoPort Inc   (United States)

^b PHARMACYCLICS INC   (United States)

Author keywords

Bioavailability; Gabapentin enacarbil; Population pharmacokinetics; Restless legs syndrome

Indexed keywords

GABAPENTIN; GABAPENTIN ENACARBIL;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; CLINICAL GLOBAL IMPRESSION SCALE; DISEASE SEVERITY; DIZZINESS; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HUMAN; INTERNATIONAL RESTLESS LEGS SCALE; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PHARMACODYNAMICS; PHARMACOKINETICS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); RESTLESS LEGS SYNDROME; SCORING SYSTEM; SEDATION; SIDE EFFECT; SLEEP QUALITY; SOMNOLENCE; STATISTICAL MODEL; SUSTAINED DRUG RELEASE; TREATMENT OUTCOME;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; AMINES; CARBAMATES; CYCLOHEXANECARBOXYLIC ACIDS; FEMALE; GAMMA-AMINOBUTYRIC ACID; HUMANS; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; PRODRUGS; RESTLESS LEGS SYNDROME; SLEEP INITIATION AND MAINTENANCE DISORDERS; YOUNG ADULT;

EID: 84863981934     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270012439209     Document Type: Article

References (31)

1. Cundy KC, Annamalai T, Bu L, et al. 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.
2. Cundy KC, Branch R, Chernov-Rogan T, et al. 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.
3. 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.
4. Lal R, Sukbuntherng J, Luo W, et al. Pharmacokinetics and tolerability of single escalating doses of gabapentin enacarbil: a randomizedsequence, double-blind, placebo-controlled crossover study in healthy volunteers. Clin Ther. 2009;31:1776-1786.
5. Lal R, Sukbuntherng J, Luo W, et al. Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine. Br J Clin Pharmacol. 2010;69:498-507.
6. Kushida CA, Walters AS, Becker P, et al. A randomized, doubleblind, placebo-controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome. Sleep. 2009;32:159-168.
7. Kushida CA, Becker PM, Ellenbogen AL, Canafax DM, Barrett RW; the XP052 Study Group. Randomized, double-blind, placebocontrolled trial of XP13512/GSK1838262 in patients with RLS. Neurology. 2009;72:439-446.
8. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4:101-119.
9. Hening W, Walters AS, Allen RP, Montplaisir J, Myers A, Ferini-Strambi L. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med. 2004;5:237-246.
10. Ondo W, Romanyshyn J, Vuong KD, Lai D. Long-term treatment of restless legs syndrome with dopamine agonists. Arch Neurol. 2004;61:1393-1397.
11. Winkelman JW, Johnston L. Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS). Sleep Med. 2004;5:9-14.
12. Dang D, Cunnington D, Swieca J. The emergence of devastating impulse control disorders during dopamine agonist therapy of the restless legs syndrome. Clin Neuropharmacol. 2011;34:66-70.
13. Rabinak CA, Nirenberg MJ. Dopamine agonist withdrawal syndrome in Parkinson disease. Arch Neurol. 2010;67:58-63.
14. Earley CJ, Silber MH. Restless legs syndrome: understanding its consequences and the need for better treatment. Sleep Med. 2010;11:807-815.
15. Stewart BH, Kugler AR, Thompson PR, Bockbrader HN. A saturable transport mechanism in 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.
16. Lal R, Sukbuntherng J, Luo W, et al. Clinical pharmacokinetics of gabapentin after administration of gabapentin enacarbil extendedrelease tablets in patients with varying degrees of renal function using data from an open-label, single-dose pharmacokinetic study. Clin Ther. 2012;34:201-213.
17. Walters AS, Ondo WG, Kushida CA, et al. Gabapentin enacarbil in restless legs syndrome: a phase 2b, two-week, randomized, double-blind, placebo-controlled trial. Clin Neuropharmacol. 2009; 32:311-320.
18. Lal R, Ellenbogen A, Chen D, et al. A randomized, double-blind, placebo-controlled, dose-response study to assess the pharmacokinetics, efficacy, and safety of gabapentin enacarbil in subjects with restless legs syndrome. Clin Neuropharmacol. In press.
19. Lee DO, Ziman RB, Perkins AT, Poceta JS, Walters AS, Barrett RW. efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome. J Clin Sleep Med. 2011;7:282-292.
20. Bogan RK, Cramer Bornemann MA, Kushida CA, Trân PV, Barrett RW, for the XP060 Study Group. Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study. Mayo Clin Proc. 2010;85:512-521.
21. World Medical Association. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. 1996 revision. http://www.wma.net/e/policy/b3.htm
22. Ekhart C, de Jonge ME, Huitema ADR, Schellens JHM, Rodenhuis S, Beijnen JH. Flat dosing of carboplatin is justified in adult patients with normal renal function. Clin Cancer Res. 2006;12:6502-6508.
23. Efron B. Bootstrap methods: another look at the jackknife. Ann Stat. 1979;7:1-26.
24. Walters AS, LeBrocq C, Dhar A, et al. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003;4:121-132.
25. Guy W. Clinical global impressions (CGI). In: Early Clinical Drug Evaluation (ECDEU) Assessment Manual for Psychopharmacology, Revised. Rockville, MD: US Department of Health, Education, and Welfare, National Institute of Mental Health, Psychopharmacology Research Branch; 1976:217-222.
26. US National Library of Medicine & National Institutes of Health. Medical encyclopedia: creatinine clearance. http://www.nlm.nih. gov/medlineplus/ency/article/003611.htm
27. Carlsson KC, van de Schootbrugge M, Eriksen HO, Moberg ER, Karlsson MO, Hoem NO. A population pharmacokinetic model of gabapentin developed in nonparametric adaptive grid and nonlinear mixed effects modeling. Ther Drug Monit. 2009;31:86-94.
28. Ouellet D, Bockbrader HN, Wesche DL, Shapiro DY, Garofalo E. Population pharmacokinetics of gabapentin in infants and children. Epilepsy Res. 2001;47:229-241.
29. Blum RA, Comstock TJ, Sica DA, et al. Pharmacokinetics of gabapentin in subjects with various degrees of renal function. Clin Pharmacol Ther. 1994;56:154-159.
30. Boyd RA, Turck D, Abel RB, Sedman AJ, Bockbrader HN. Effects of age and gender on single-dose pharmacokinetics of gabapentin. Epilepsia. 1999;40:474-479.
31. McLean MJ. Gabapentin. Epilepsia. 1995;36(suppl 2):S73-S86.