Abstracts

RATIONALE: Gabapentin (GBP) displays dose dependent,oral absorption, most likely due to saturation of System L. Although previous experiments have suggested that various foods/meals do not impair the absorption of GBP capsules, there are no data regarding concomitant administration with enteral feeding supplements. Recently, a new formulation of this AED, GBP syrup,has been developed. Given the utility of this agent, it is likely to be used in a variety of patient populations including children and the elderly. It is also reasonable to speculate that in these patients, alternative administration techniques such as mixing with various liquids/beverages may be required. The objective of this study was to evaluate the oral absorption profile of this new formulation following concomitant administration with vehicles of varied macronutrient content including grape juice, chocolate milk and an enteral nutrition supplement, Sustacal.
METHODS: This study used an unblinded, randomized, cross-over design.Following an overnight fast, a single-dose of 500mg (GBP syrup 50mg/ml) was mixed with either 120ml tap water (control, phase I), 120ml grape juice (phase II), 120ml chocolate milk (phase III), or 240ml Sustacal (phase IV). A 7 day washout period occured between each study phase. Serial blood samples were obtained over 24hrs in order to determine GBP serum concentrations (HPLC). Calculated pharmacokinetic variables included area under the concentration-time curve (AUC), maximun serum concentration (Cmax) and time to maximum serum concentration (Tmax) using standard non-compartmental methods.Statistical analysis included ANOVA with significance assigned at p[lt]0.05.
RESULTS: N= 10 adult healthy volunteers (9 women/1 man)were evaluated (mean age and weight were 29.1 years and 76.24 kg, respectively).AUC values for study phases I-IV were 29.4[plusminus]10.1, 33.2[plusminus]7.4,38.1[plusminus]12.1 and 36.6[plusminus]15.5 [mu]g/ml*hr, respectively. A Significant increase in AUC (31%)was noted in phase III -chocolate milk as compared to phase I-control.Cmax values for phase I-IV were 3.3 [plusminus]1.2, 3.5[plusminus]0.7, 4.2[plusminus]0.86, and 4.1[plusminus]1.5[mu]g/ml, respectively. No significant differences were noted between control and any other study phase.Similarly, no significant differences in Tmax were seen between any study phase.
CONCLUSIONS: Concomitant administration of GBP syrup with various liquid foods/beverages, including a common nutritional supplement, does not result in impaired drug absorption. Interestingly, similar to previous studies with GBP capsules (Gidal BE et al Ann Pharmacother 1998;32:405-9),these data suggest that at least at the doses studied, dietary macronutrient content (i.e. milk protein) may favorably influence GBP absorption.
Support: Pfizer
Disclosure: Grant - Pfizer, GlaxoSmithKline, Abbott; Honoraria - Pfizer,GlaxoSmithKline,Abbott,UCB-Pharma,Ortho-McNeil