title: Enteral, oral, and rectal absorption of ceftriaxone using glyceride enhancers.
abstract: In vivo models in rodents and primates were used to investigate ways of overcoming the poor oral and rectal absorption of ceftriaxone. The sodium salt of ceftriaxone at 20 mg/kg was formulated in C8-C10 chain length, mono- and diglyceride extracts of coconut oil (Capmul) and administered intraduodenally to adult rats. Peak plasma levels of 17-52 micrograms/ml and bioavailability averaging 38% were attained. Significant plasma levels (42-45 micrograms/ml) were also demonstrated in squirrel monkeys with doses of 20 mg/kg ceftriaxone formulated in Capmul and given by the enteral route. Enteric-coated capsules containing this formulation were also orally administered to squirrel monkeys and gave high plasma levels (10-31 micrograms/ml) between 1 and 6 h following dosing. In rectal absorption studies, ceftriaxone formulated in Capmul as a suspension gave peak blood levels of 62-84 micrograms/ml (average bioavailability 42%) in the rabbit. In the baboon, rectal administration of ceftriaxone formulated with Capmul in a Witepsol H15 suppository gave Cmax levels ranging from 9 to 48 micrograms/ml, depending on the dose of the antibiotic and the drug/enhancer ratio.
authors.affiliation: Department of Pharmacology, Hoffmann-La Roche Inc., Nutley, N.J.
authors.forename: G
authors.initials: G
authors.lastname: Beskid
authors.forename: J
authors.initials: J
authors.lastname: Unowsky
authors.forename: C R
authors.initials: CR
authors.lastname: Behl
authors.forename: J
authors.initials: J
authors.lastname: Siebelist
authors.forename: J L
authors.initials: JL
authors.lastname: Tossounian
authors.forename: C M
authors.initials: CM
authors.lastname: McGarry
authors.forename: N H
authors.initials: NH
authors.lastname: Shah
authors.forename: R
authors.initials: R
authors.lastname: Cleeland
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D002443:Ceftriaxone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005989:Glycerides / Q000494:pharmacology; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects; D010215:Papio; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum / Q000378:metabolism*; D012453:Saimiri
chemical_list: D005989:Glycerides; D002443:Ceftriaxone