Gabapentin bioavailability: effect of dose and frequency of administration in adult patients with epilepsy

Gabapentin (GBP) is a non-metabolized antiepileptic drug that is eliminated by renal excretion and displays saturable, dose dependent absorption. The recommended dosing schedule for GBP is t.i.d. At large daily doses, oral bioavailability (F) may be improved by giving the daily dose more frequently. Objective: To evaluate whether switching GBP dosage regimen from t.i.d. to q.i.d. results in increased oral bioavailability. Methods: This study consisted of two parts; a computer simulated pharmacokinetic model and a clinical pharmacokinetic study in nine adult epileptic patients receiving 3600 mg/day and 11 receiving 4800 mg/day. All patients were evaluated during both t.i.d. and q.i.d. regimens. F were determined by calculation of percent of dose excreted unchanged using steady-state 24-h urine collections and were compared using a paired t-test. Results: At 3600 mg/day, mean F following t.i.d. and q.i.d. dosing were 38.7 +/- 22.1% and 40.0 +/- 18.9%, respectively (P = 0.738). At 4800 mg/day, mean F following t.i.d. and q.i.d. dosing were 29.2 +/- 16.2% and 35.6 +/- 17.6%, respectively (P = 0.006). Discussion: Good agreement was observed between values from this study and predicted values based on the pharmacokinetic model. Improved GBP F at doses of 3600 mg/day was not achieved with more frequent drug administration, and thus is not warranted. At 4800 mg/day, a 22% increase in F was observed with more frequent drug dosing. Conclusion: GBP F may be significantly increased by q.i.d. versus t.i.d. dosing, depending upon dose level. This increase in F however must be balanced against the inconvenience of more frequent dosing. Therapeutic drug level monitoring may aid in the evaluation of such pharmacokinetic maneuvers. (C) 1998 Elsevier Science B.V. All rights reserved.