Ceftriaxone Absorption Enhancement for Noninvasive Administration as an Alternative to Injectable Solutions

ABSTRACT Neonatal sepsis is a major cause of infant mortality in developing countries because of delayed injectable treatment, making it urgent to develop noninjectable formulations that can reduce treatment delays in resource-limited settings. Ceftriaxone, available only for injection, needs absorption enhancers to achieve adequate bioavailability via nonparenteral administration. This article presents all available data on the nonparenteral absorption of ceftriaxone in humans and animals, including unpublished work carried out by F. Hoffmann-La Roche (Roche) in the 1980s and new data from preclinical studies with rabbits, and discusses the importance of these data for the development of noninjectable formulations for noninvasive treatment. The combined results indicate that the 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 a maximal plasma concentration of 21 µg/ml with good tolerance in human subjects. The rabbit model developed can also be used to screen for the bioavailability of other formulations before assessment in humans.

Effect of Rectal Levodopa Administration: A Case Report

Objective: The aim of this report is to discuss whether or not rectal levodopa administration is useful in some situations. Background: In situations where oral intake of levodopa formulations is not possible, the treatment options of Parkinson's disease patients are limited. The literature describes no or low rectal absorption of levodopa. Case Description: A patient with an ileus was unable to take oral medication. After consulting the neurologist and pharmacist, the surgeon decided to describe a rectal formulation of levodopa/carbidopa (100/25 mg) once daily. On day 3 of the therapy, 1 h after administration of the rectal formulation of levodopa/carbidopa, a blood sample was drawn. The patient was unable to take his other Parkinson medication; therefore the dose of the rectal levodopa/carbidopa was increased to 5 times a day. Results: Full control of the symptoms was not achieved, but alleviation of the most severe tremor and rigidity was seen, which was confirmed by the neurologist, nurses and patient. The levodopa concentration detected was 17 nmol/l. Compared to levodopa concentrations described in the literature (1,400-12,000 nmol/l), the concentration is very low. There are some possible explanations for the low concentration detected. The presence of a specific amino acid transport system in the rectum is not known, which could lead to no or reduced absorption. The poor rectal absorption of carbidopa leads to a higher conversion of levodopa to dopamine peripherally. Conclusions: In situations where patients are unable to take oral medication, rectal administration of levodopa/carbidopa is worth considering.

Self-Administered Ethanol Enema Causing Accidental Death

Excessive ethanol consumption is a leading preventable cause of death in the United States. Much of the harm from ethanol comes from those who engage in excessive or hazardous drinking. Rectal absorption of ethanol bypasses the first pass metabolic effect, allowing for a higher concentration of blood ethanol to occur for a given volume of solution and, consequently, greater potential for central nervous system depression. However, accidental death is extremely rare with rectal administration. This case report describes an individual with klismaphilia whose death resulted from acute ethanol intoxication by rectal absorption of a wine enema.