Enhanced oral bioavailability of poorly absorbed drugs. I. Screening of absorption carrier for the ceftriaxone complex.

In this study, we attempted to improve the oral absorption of ceftriaxone (CTX) by using an absorption carrier and the CTX complex together. After the CTX-Ca-carrageenan gel complex was prepared, several kinds of compounds (Capmul MCM C10, Gelucire 44/14, glycyrrhizin) were screened as potential oral enhancers for our experiment and the intestinal morphologies in rats were examined. Of these compounds, the mono- and diglyceride mixtures, Capmul MCM C10 greatly enhanced the gastrointestinal absorption of CTX when this carrier was coadministered with the complex in rats. Percent bioavailability was attained in rats by the enteral route ranging from 55 to 79% when this complex was administered with various doses of Capmul MCM C10. Furthermore, the surface morphology of the complex has a highly smooth appearance as seen under scanning electron microscopy after preparation. No treatment-related signs of any damage were observed on the administrations intestinal membrane when morphologies were examined in rats after the complex and the absorption carrier were coadministered. The results of the observation suggest that Capmul MCM C10 is a promising carrier, having a good balance between bioavailability enhancing activity and safety, for the oral delivery of CTX when it is coadministered with complex.

[1]  E. A. Carr,et al.  Uptake and translocation of microparticles in small intestine , 1995, Digestive Diseases and Sciences.

[2]  C. Pidgeon,et al.  Intestinal Peptide Transport Systems and Oral Drug Availability , 1999, Pharmaceutical Research.

[3]  P. Artursson,et al.  Mechanism of Absorption Enhancement in Humans After Rectal Administration of Ampicillin in Suppositories Containing Sodium Caprate , 1997, Pharmaceutical Research.

[4]  Harma Ellens,et al.  Effect of Medium-Chain Glycerides on Physiological Properties of Rabbit Intestinal Epithelium in Vitro , 1994, Pharmaceutical Research.

[5]  W. Curatolo,et al.  Intestinal Permeability Enhancement: Efficacy, Acute Local Toxicity, and Reversibility , 1994, Pharmaceutical Research.

[6]  E. LeCluyse,et al.  Enhanced Bioavailability of Cefoxitin Using Palmitoylcarnitine. II. Use of Directly Compressed Tablet Formulations in the Rat and Dog , 1993, Pharmaceutical Research.

[7]  Toshiharu Horie,et al.  Enhancement of Colonic Drug Absorption by the Transcellular Permeation Route , 1988, Pharmaceutical Research.

[8]  J. Dressman,et al.  In vitro-in vivo correlations for lipophilic, poorly water-soluble drugs. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[9]  B. Aungst,et al.  Intestinal permeation enhancers. , 2000, Journal of pharmaceutical sciences.

[10]  P. Sinko,et al.  The effect of physical barriers and properties on the oral absorption of particulates. , 1998, Advanced drug delivery reviews.

[11]  C. Price,et al.  Lipid-based delivery systems for improving the bioavailability and lymphatic transport of a poorly water-soluble LTB4 inhibitor. , 1998, Journal of pharmaceutical sciences.

[12]  P. Artursson,et al.  Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells. , 1998, The Journal of pharmacology and experimental therapeutics.

[13]  A. Dantzig.  Oral absorption of β-lactams by intestinal peptide transport proteins , 1997 .

[14]  T. Kimura,et al.  Mechanism of gastrointestinal absorption of glycyrrhizin in rats. , 1994, Biological & pharmaceutical bulletin.

[15]  J. Hochman,et al.  In vitro and in vivo analysis of the mechanism of absorption enhancement by palmitoylcarnitine. , 1994, The Journal of pharmacology and experimental therapeutics.

[16]  T. Yotsuyanagi,et al.  Effect of glycyrrhizinate on dissolution behavior and rectal absorption of amphotericin B in rabbits. , 1992, Chemical & pharmaceutical bulletin.

[17]  Thomas R. Tice,et al.  Controlled vaccine release in the gut-associated lymphoid tissues. I. Orally administered biodegradable microspheres target the peyer's patches , 1990 .

[18]  R. Quintiliani,et al.  Clinical Pharmacokinetics of Ceftriaxone , 1989, Clinical pharmacokinetics.

[19]  D. Bourne,et al.  Disposition of ceftriaxone in rat: application of a pharmacokinetic-protein binding model and comparison with cefotaxime. , 1989, Xenobiotica; the fate of foreign compounds in biological systems.

[20]  A. Serajuddin,et al.  Effect of vehicle amphiphilicity on the dissolution and bioavailability of a poorly water-soluble drug from solid dispersions. , 1988, Journal of pharmaceutical sciences.

[21]  D. Bourne,et al.  High-performance liquid chromatographic assay of cefotaxime, desacetylcefotaxime and ceftriaxone in rat plasma. , 1988, Journal of chromatography.

[22]  J. Tossounian,et al.  Enteral, oral, and rectal absorption of ceftriaxone using glyceride enhancers. , 1988, Chemotherapy.

[23]  T. Beam.  Ceftriaxone: A Beta‐lactamase—stable, Broad‐spectrum Cephalosporin with an Extended Half‐life , 1985, Pharmacotherapy.

[24]  M Sekine,et al.  Improvement of bioavailability of poorly absorbed drugs. II. Effect of medium chain glyceride base on the intestinal absorption of cefmetazole sodium in rats and dogs. , 1984, Journal of pharmacobio-dynamics.

[25]  Fung Kp,et al.  Pharmacokinetics of ceftriaxone after intravenous infusion and intramuscular injection. , 1984 .

[26]  I. Patel,et al.  Pharmacokinetic profile of ceftriaxone in man. , 1984, The American journal of medicine.