Pharmacokinetics of immediate release, extended release, and gastric retentive gabapentin formulations in healthy adults
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Abstract

OBJECTIVE:

Gabapentin immediate release (GBP-IR), gabapentin gastric retentive (GBP-GR), and the prodrug gabapentin enacarbil extended release formulation (GEn) have been approved for management of postherpetic neuralgia (PHN) in adults. This is the first pharmacokinetic (PK) comparison of all three formulations using FDA-recommended doses for PHN.

MATERIALS:

This study compared the steady-state PK of GBP-IR 600 mg t.i.d., GBP-GR 1,800 mg q.d., and GEn 600 mg b.i.d. in healthy adults.

METHODS:

The open-label study consisted of a 3-day lead-in of escalating doses of GBP-IR, 5 days of treatment with each formulation (GPB-IR, GPB-GR, and GEn), and a 7-day taper period on 600 mg GEn q.d.. Plasma concentrations were collected on day 5 for each formulation. PK parameters were estimated from plasma concentration data.

RESULTS:

14 healthy subjects (7 men, 7 women; mean (SD) age, 46.8 (7.60) years; mean (SD) body mass index, 26.7 (1.7) kg/m2) received all doses and completed the study. GBP-GR resulted in substantially (~ 4-fold) higher peak-to-trough ratio and percent fluctuation compared to GEn. GEn resulted in more sustained and less fluctuating daily exposure relative to GBP-IR, particularly at the end of 24 hours of dosing. In contrast, gabapentin fluctuation from GBP-IR consisted of 3 distinct peaks. After dose normalization, gabapentin exposure with GEn was ~ 2.2-fold and ~ 1.4-fold higher compared to GBP-GR and GBP-IR, respectively. All treatments were well tolerated.

CONCLUSION:

GEn requires less frequent dosing compared with GBP-IR and fluctuates less with sustained gabapentin exposure throughout the day. These PK differences may have clinically relevant implications.
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• Authors: Dennis Swearingen, Gerald M Aronoff, Sabrina Ciric, Ritu Lal
• Journal: International journal of clinical pharmacology and therapeutics (Int J Clin Pharmacol Ther) Vol. 56 Issue 5 Pg. 231-238 (May 2018) ISSN: 0946-1965 [Print] Germany
• PMID: 29633699 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Amines
• Analgesics
• Cyclohexanecarboxylic Acids
• Delayed-Action Preparations
• gamma-Aminobutyric Acid
• Gabapentin

Topics

• Administration, Oral
• Adult
• Amines (administration & dosage, blood, chemistry, pharmacokinetics)
• Analgesics (administration & dosage, blood, chemistry, pharmacokinetics)
• Biological Availability
• Cyclohexanecarboxylic Acids (administration & dosage, blood, chemistry, pharmacokinetics)
• Delayed-Action Preparations
• Drug Compounding
• Drug Monitoring
• Female
• Gabapentin
• Healthy Volunteers
• Humans
• Male
• Middle Aged
• Models, Biological
• Therapeutic Equivalency
• gamma-Aminobutyric Acid (administration & dosage, blood, chemistry, pharmacokinetics)