Pharmacokinetic analysis of 6-monoamino-beta-cyclodextrin after intravenous or oral administration to rats using a specific enzyme immunoassay

We have developed a highly sensitive enzyme immunoassay for 6-monoamino-bet a-CD (mono(6-amino-6-deoxy)cyclomaltoheptaose) and its parent compound (bet a-CD) with a detection limit in the 100 pg/mL range. The polyclonal antibod ies obtained are highly specific for the beta-cyclodextrin core and do not recognize other cyclic cyclodextrins (i.e., alpha- and gamma-CD) or linear analogues. This enzyme immunoassay can be used to quantify 6-monoamino-beta -CD in rat urine and plasma. Using this immunoassay, we have evaluated the main pharmacokinetic parameters of 6-monoamino-beta-CD after iv administrat ion to the rat of a 25 mg/kg dose. Since this method is strictly specific t o the native beta-CD form, we have demonstrated that the molecule rapidly d isappeared from plasma but is probably distributed in the tissues. The urin ary route appears as the predominant way of elimination since almost all th e administered drug is recovered in urine. Finally, analysis of the same mo lecule after oral administration to the rat (25 mg/kg) demonstrates low pla sma levels and that about 1% of the administered dose is excreted in urine. These experiments demonstrate the high stability of the beta-CD core irres pective of the method of administration. This immunological method could pr ovide relevant information on the fate of beta-CD and some derivatives for drug delivery using different modes of administration (oral, parenteral, tr ansmucosal, or dermal).