Relative bioavailability of crushed tebipenem administered through a nasogastric tube with and without enteral feeding

Abstract

Abstract Objective Tebipenem pivoxil hydrobromide is an orally bioavailable carbapenem prodrug of the active agent tebipenem with broad-spectrum activity against drug-resistant Enterobacterales. This study aimed to evaluate the relative bioavailability of crushed tebipenem tablets administered via nasogastric tube (NGT) with or without concomitant enteral feeds. Methods This Phase 1, open label study randomized 12 healthy subjects to receive a crushed tebipenem tablet via NGT (n = 6) or via NGT with concomitant Osmolite® enteral feeds (n = 6) on Study Day 1, followed by oral administration of tebipenem whole tablet (reference formulation) on Study Day 2. Tebipenem plasma concentrations were measured by LC with mass spectrometry. Bioequivalence was determined using pharmacokinetic parameters derived through non-compartmental analyses. Results Mean ± SD tebipenem pharmacokinetic parameters in plasma for subjects who received a crushed tablet via NGT (relative to whole tablet) and a crushed tablet with enteral feeds (relative to whole tablet) were as follows: maximum total plasma concentration (Cmax), 11.1 ± 3.9 (12 ± 3.4) and 10.2 ± 1.9 (10 ± 4) mg/L; area under the curve (AUC0–8), 17.5 ± 3.5 (17.9 ± 2.3) and 15 ± 4.3 (13.4 ± 5.3) mg•h/L. Using the 90% CI criteria, Cmaxand AUC0–8 values for tebipenem were found to be bioequivalent following alternative methods of administration compared with oral dosing of the whole tablet. The three methods of administration were well tolerated. Conclusion Results demonstrate that tebipenem maintained bioequivalence when crushed and administered via NGT with and without accompanying enteral feeds in healthy subjects, relative to whole tablet oral administration. Data therefore support alternative methods of tebipenem administration depending on patient condition.