Absorption, distribution and excretion of galactosyl-beta-cyclodextrin and mannosyl-beta-cyclodextrin in rats.
Microanalytical methods were developed for measuring galactosyl-beta-cyclodextrin (Gal-betaCD) and mannosyl (Man)-betaCD in biological matrices of the rat by HPLC with pulsed amperometric detection. Then, using these methods, the absorption, distribution and excretion of intravenously and orally administered Gal-betaCD and Man-betaCD were determined in rats, and compared with those of glucosyl (Glc)-betaCD. The pharmacokinetic behavior of Gal-betaCD, Man-betaCD and Glc-betaCD after intravenous administration (50 mg/kg) was very similar. Within 6 h after intravenous administration, unchanged Gal-betaCD and Man-betaCD recovered in urine accounted for about 90% of each dose. After oral administration (500 mg/kg), 0.37% and 0.38% of Gal-betaCD and Man-betaCD, respectively, were excreted in urine. After intravenous and oral administration of Gal-betaCD and Man-betaCD, the decomposition of Gal-betaCD and Man-betaCD to betaCD in the urine, kidney and liver was greater than that of Glc-betaCD. The sum of the molar concentrations of branched CDs and their decomposition product, betaCD, in the liver at 4 h after intravenous administration of Gal-betaCD and Man-betaCD was greater than that of Glc-betaCD. Furthermore, the inclusion complexes of estriol and betamethasone with Gal-betaCD, Man-betaCD and Glc-betaCD were prepared and their absorption was evaluated after oral administration in rats. The plasma concentrations of the drugs after oral administration of drug-Gal-betaCD and drug-Man-betaCD complexes were the same as those after the administration of drug-Glc-betaCD complexes.
Kubota
Y
Y
School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Sanbe
H
H
Koizumi
K
K
D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D004337:Drug Carriers; D004563:Electrochemistry; D005690:Galactose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000652:urine; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008358:Mannose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D003505:Cyclodextrins; D004337:Drug Carriers; D008358:Mannose; D005690:Galactose