Inter- and intra-subject variability in gabapentin absorption and absolutebioavailability

Gabapentin (GBP) is a non-metabolized, Iron-plasma protein bound, renally e xcreted antiepileptic drug that is actively absorbed via the system L amino acid transporter. Previous studies have demonstrated that,gabapentin displ ays dose-dependent absorption. Objectives: These studies were conducted to determine inter- and intra-subject variability of gabapentin absorption. Tw o prospective clinical studies in healthy adult volunteers were conducted. Coefficient of variation (CV) was used to express variability of gabapentin absorption. Methods: Study A: 400-mg single dose, randomized, cross-over s tudy to assess bioavailability of four different gabapentin formulations (n = 20, 9 males, 11 females; mean age and weight 41 years, 75.1 kg). Plasma was serially collected up to 48 h and bioavailability (F) calculated post-d ose to determine concentration-time curves (AUC). All four formulations wer e bioequivalent, thus repeated measures analysis was performed to assess in ter-and intra-subject variability. Study B: 600-mg single dose study (n = 5 0, 15 males, 35 females; mean age and weight 31.1 years, 72.7 kg) was condu cted to determine inter-subject variability in gabapentin F. Urine was coll ected over 48 h and bioavailability (F) calculated. Urine and plasma gabape ntin concentrations were measured by HPLC-UV. Results : Study A: Overall me an (CV) of GBP AUC values was 34.1 +/- 24 mu g/h per ml. Inter-subject CV f or AUC was 22.5% and intra-subject CV was 12.1%. Study B: Overall mean (SD) GBP F was 49.3 +/- 13.6%. Inter-subject CV of F was 27.6%. Discussion: The inter-subject variability in gabapentin absorption is substantially less t han that of the inter-subject variability. This indicates that one would ex pect a wide range in gabapentin absorption between subjects; however, a muc h smaller variability within a subject. The within subject variability of g abapentin is small enough that plasma drug monitoring may be used to assess gabapentin absorption for a given subject and the benefit of dose individu alization. (C) 2000 Elsevier Science B.V. All rights reserved.