Clinical Pharmacokinetics of Gabapentin After Administration of Gabapentin Enacarbil Extended-Release Tablets in Patients With Varying Degrees of Renal Function Using Data From an Open-Label, Single-Dose Pharmacokinetic Study

Clinical Therapeutics

Volumn 34, Issue 1, 2012, Pages 201-213

  Lal, Ritu ^a   Sukbuntherng, Juthamas ^b   Luo, Wendy ^a   Chen, Dan ^a   Blumenthal, Robin ^c   Ho, Judy ^a   Cundy, Kenneth C ^a  

^a XenoPort Inc   (United States)

^b PHARMACYCLICS INC   (United States)

^c PFIZER INC   (United States)

Author keywords

End stage renal disease; Gabapentin enacarbil; Population pharmacokinetics; Renal impairment; Restless legs syndrome

Indexed keywords

CREATINE; GABAPENTIN; GABAPENTIN ENACARBIL;

ADULT; AFRICAN AMERICAN; AGED; AMERICAN INDIAN; ARTICLE; ASTHENIA; BODY MASS; CELLULITIS; CLINICAL ARTICLE; CREATININE CLEARANCE; DEFECATION URGENCY; DIALYSATE; DISEASE SEVERITY; DIZZINESS; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; ECHOCARDIOGRAPHY; FALLING; FEMALE; FLATULENCE; GLOMERULUS FILTRATION RATE; HEMODIALYSIS; HUMAN; HYPERKALEMIA; HYPERTENSION; KIDNEY DISEASE; KIDNEY FAILURE; KIDNEY FUNCTION; MALE; MAXIMUM PLASMA CONCENTRATION; MUSCLE WEAKNESS; OPEN STUDY; PAIN; PANCYTOPENIA; SEDATION; SIDE EFFECT; SINGLE DRUG DOSE; TABLET; THROMBOCYTOPENIA; TIME TO MAXIMUM PLASMA CONCENTRATION; UNITED STATES; URINALYSIS; VITAL SIGN; XEROSTOMIA;

ADMINISTRATION, ORAL; ADULT; AGED; ANALGESICS; ANTICONVULSANTS; BIOLOGICAL MARKERS; BIOTRANSFORMATION; CARBAMATES; CREATININE; DELAYED-ACTION PREPARATIONS; FEMALE; FLORIDA; GAMMA-AMINOBUTYRIC ACID; HUMANS; HYDROLYSIS; KIDNEY; KIDNEY DISEASES; KIDNEY FAILURE, CHRONIC; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; MINNESOTA; MODELS, BIOLOGICAL; PRODRUGS; RENAL DIALYSIS; SEVERITY OF ILLNESS INDEX; TABLETS;

EID: 84862919572     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2011.12.004     Document Type: Article

References (34)

1. Beydoun A., Uthman B.M., Sackellares J.C. Gabapentin: pharmacokinetics, efficacy, and safety. Clin Neuropharmacol 1995, 18:469-481.
2. Rice A.S., Maton S. Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo controlled study. Pain 2001, 94:215-224.
3. Rowbotham M., Harden N., Stacey B., et al. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA 1998, 280:1837-1842.
4. Gabapentin in partial epilepsy. Lancet 1990, 335:1114-1117. UK Gabapentin Study Group.
5. Gabapentin as add-on therapy in refractory partial epilepsy: a double-blind, placebo-controlled, parallel-group study. Neurology 1993, 43:2292-2298. US Gabapentin Study Group No. 5.
6. Anhut H., Ashman P., Feuerstein T.J., et al. Gabapentin (Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. Epilepsia 1994, 35:795-801. International Gabapentin Study Group.
7. Appleton R., Fichtner K., LaMoreaux L., et al. Gabapentin as add-on therapy in children with refractory partial seizures: a 12-week, multicentre, double-blind, placebo-controlled study. Epilepsia 1999, 40:1147-1154. Gabapentin Paediatric Study Group.
8. McLean M.J. Gabapentin in the management of convulsive disorders. Epilepsia 1999, 40(Suppl 6):S39-S50.
9. Stewart B.H., Kugler A.R., Thompson P.R., et al. 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.
10. Uchino H., Kanai Y., Kim D.K., et al. 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.
11. Gidal B.E., DeCerce J., Bockbrader H.N., et al. Gabapentin bioavailability: effect of dose and frequency of administration in adult patients with epilepsy. Epilepsy Res 1998, 31:91-99.
12. Gidal B.E., Radulovic L.L., Kruger S., et al. Inter- and intra-subject variability in gabapentin absorption and absolute bioavailability. Epilepsy Res 2000, 40:123-127.
13. Vollmer K.O., von Hodenberg A., Kolle E.U. Pharmacokinetics and metabolism of gabapentin in rat, dog and man. Arzneimittelforschung 1986, 36:830-839.
14. Bockbrader H.N., Breslin E.M., Underwood B.A., et al. Multiple-dose, dose-proportionality study of Neurontin (gabapentin) in healthy volunteers [abstract]. Epilepsia 1996, 37. 159-159.
15. Cundy K.C., 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.
16. Cundy K.C., Annamalai T., Bu L., et al. XP13512 [(±)-1-([(alpha-isobutanoyloxyethoxy)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.
17. Cundy K.C., Sastry S., Luo W., et al. Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin. J Clin Pharmacol 2008, 48:1378-1388.
18. Lal R., Sukbuntherng J., Luo W., et al. Pharmacokinetics of single escalating doses of gabapentin enacarbil in healthy adult volunteers: a randomized sequence, double-blind, placebo-controlled, crossover study. Clin Ther 2009, 31:1776-1786.
19. Kushida C.A., Becker P.M., Ellenbogen A.L., et al. Randomized, double-blind, placebo-controlled trial of XP13512/GSK1838262 in patients with RLS. Neurology 2009, 72:439-446.
20. Kushida C.A., Walters A.S., Becker P., et al. A randomized, double-blind, placebo-controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome. Sleep 2009, 32:159-168.
21. Allen R.P., Picchietti D., Hening W.A., et al. 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.
22. Blum R.A., Comstock T.J., Sica D.A., et al. Pharmacokinetics of gabapentin in subjects with various degrees of renal function. Clin Pharmacol Ther 1994, 56:154-159.
23. Wong M.O., Eldon M.A., Keane W.F., et al. Disposition of gabapentin in anuric subjects on hemodialysis. J Clin Pharmacol 1995, 35:622-626.
24. Guidance for industry pharmacokinetics in patients with impaired renal function: study design, data analysis, and impact on dosing and labeling US Food and Drug Administration, Accessed April 26, 2011. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072127.pdf.
25. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects [revision]. Presented at the 48th World Medical Association General Assembly; October 22-26, 1996; Somerset West, Republic of South Africa. Accessed August 13, 2010. http://www.wma.net/e/policy/b3.htm.
26. Cockcroft D.W., Gault M.H. Prediction of creatinine clearance from serum creatinine. Nephron 1976, 16:31-41.
27. Gibaldi M., Perrier D. Pharmacokinetics 1982, Marcel Dekker, Inc, New York, NY.
28. Brody S.R., Humphreys M.H., Gambertoglio J.G., et al. Pharmacokinetics of cidofovir in renal insufficiency and in continuous ambulatory peritoneal dialysis or high-flux hemodialysis. Clin Pharmacol Ther 1999, 65:21-28.
29. 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.
30. Walters A.S., Ondo W.G., Kushida C.A., 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.
31. Bogan R.K., Cramer Bornemann M.A., Kushida C.A., et al. Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study. Mayo Clin Proc 2010, 85:512-521.
32. McLean M.J. Gabapentin. Epilepsia 1995, 36(Suppl 2):S73-S86.
33. Ouellet D., Bockbrader H.N., Wesche D.L., et al. Population pharmacokinetics of gabapentin in infants and children. Epilepsy Res 2001, 47:229-241.
34. Zand L., McKian K.P., Qian Q. Gabapentin toxicity in patients with chronic kidney disease: a preventable cause of morbidity. Am J Med 2010, 123:367-373.