Ceftriaxone absorption enhancement for noninvasive administration as an alternative to injectable solutions [Clinical Therapeutics]

Neonatal sepsis is a major cause of infant mortality in developing countries because of delayed injectable treatment, making it urgent to develop non-injectable formulations that can reduce treatment delays in resource limited settings. Ceftriaxone, available only for injection, needs absorption enhancers to achieve adequate bioavailability via non-parenteral administration. This article presents all available ceftriaxone human and animal non-parenteral absorption data, including unpublished work carried out by F. Hoffmann-La Roche (Roche) in the 1980s and new rabbit pre-clinical data and discusses the importance of these data for the development of non-injectable formulations for non-invasive treatment. The combined results indicate that rectal absorption of ceftriaxone is feasible and likely to lead to a bioavailable formulation that can reduce treatment delays in neonatal sepsis. A bile salt, Chenodeoxycholate sodium salt (Na-CDC) used as an absorption enhancer at a 125 mg dose together with a 500 mg dose of ceftriaxone, provided 24% rectal absorption of ceftriaxone and Cmax of 21 µg/ml with good tolerance in human subjects. The rabbit model developed can also be used to screen for bioavailability of other formulations before human assessment.

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