Inter- and intra-subject variability in gabapentin absorption and absolute bioavailability

• Published in: Epilepsy research Vol. 40; no. 2; pp. 123 - 127
• Main Authors: Gidal, Barry E., Radulovic, L.L., Kruger, Sarah, Rutecki, Paul, Pitterle, Michael, Bockbrader, Howard N.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.07.2000; Elsevier
• Subjects: Absorption; Acetates - blood; Acetates - pharmacokinetics; Acetates - urine; Adult; Amines; Analysis of Variance; Anticonvulsants - blood; Anticonvulsants - pharmacokinetics; Anticonvulsants - urine; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Cross-Over Studies; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Drug Monitoring; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Medical sciences; Middle Aged; Neuropharmacology; Non-metabolized; Pharmacology. Drug treatments; Prospective Studies; Gabapentin; Non-metabolized; Absorption; Human; Intraindividual comparison; Interindividual comparison; Anticonvulsant; Bioavailability; Metabolism; Pharmacokinetics
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/S0920-1211(00)00117-0

Gabapentin (GBP) is a non-metabolized, non-plasma protein bound, renally excreted antiepileptic drug that is actively absorbed via the system L amino acid transporter. Previous studies have demonstrated that gabapentin displays dose-dependent absorption. Objectives: These studies were conducted to determine inter- and intra-subject variability of gabapentin absorption. Two 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 study 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-dose to determine concentration-time curves ( AUC). All four formulations were bioequivalent, thus repeated measures analysis was performed to assess inter-and intra-subject variability. Study B: 600-mg single dose study ( n=50, 15 males, 35 females; mean age and weight 31.1 years, 72.7 kg) was conducted to determine inter-subject variability in gabapentin F. Urine was collected over 48 h and bioavailability (F) calculated. Urine and plasma gabapentin concentrations were measured by HPLC-UV. Results: Study A: Overall mean ( CV) of GBP AUC values was 34.1±24 ug/h per ml. Inter-subject CV for 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 than that of the inter-subject variability. This indicates that one would expect a wide range in gabapentin absorption between subjects; however, a much smaller variability within a subject. The within subject variability of gabapentin is small enough that plasma drug monitoring may be used to assess gabapentin absorption for a given subject and the benefit of dose individualization.