Absorption, distribution and excretion of galactosyl-beta-cyclodextrin andmannosyl-beta-cyclodextrin in rats

Microanalytical methods were developed for measuring galactosyl-beta-cyclod extrin (Gal-beta CD) and mannosyl (Man)-beta CD in biological matrices of t he rat by HPLC with pulsed amperometric detection. Then, using these method s, the absorption, distribution and excretion of intravenously and orally a dministered Gal-beta CD and Man-beta CD were determined in rats, and compar ed with those of glucosyl (Glc)-beta CD. The pharmacokinetic behavior of Ga l-beta CD, Man-beta CD and Glc-beta CD after intravenous administration (50 mg/kg) was very similar. Within 6 h after intravenous administration, unch anged Gal-beta CD and Man-beta CD recovered in urine accounted for about 90 % of each dose. After oral administration (500 mg/kg), 0.37% and 0.38% of G al-beta CD and Man-beta CD, respectively, were excreted in urine. After int ravenous and oral administration of Gal-beta CD and Man-beta CD, the decomp osition of Gal-beta CD and Man-beta CD to beta CD in the urine, kidney and liver was greater than that of Glc-beta CD. The sum of the molar concentrat ions of branched CDs and their decomposition product, beta CD, in the liver at 4 h after intravenous administration of Gal-beta CD and Man-beta CD was greater than that of Glc-beta CD. Furthermore, the inclusion complexes of estriol and betamethasone with Gal-beta CD, Man-beta CD and Glc-beta CD wer e prepared and their absorption was evaluated after oral administration in rats. The plasma concentrations of the drugs after oral administration of d rug-Gal-beta CD and drug-Man-beta CD complexes were the same as those after the administration of drug-Glc-beta CD complexes.