Enteral, oral, and rectal absorption of ceftriaxone using glyceride enhancers.
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.
Beskid
G
G
Department of Pharmacology, Hoffmann-La Roche Inc., Nutley, N.J.
Unowsky
J
J
Behl
C R
CR
Siebelist
J
J
Tossounian
J L
JL
McGarry
C M
CM
Shah
N H
NH
Cleeland
R
R
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
D005989:Glycerides; D002443:Ceftriaxone