title: Does the Digestibility of Cyclodextrins Influence the In Vivo Absorption of Benzo[a]pyrene in Rats?
abstract: An important excipient used to overcome poor solubility is cyclodextrin. However, data in the literature suggest that excessive overdosing of cyclodextrins can decrease the absorption of compounds administered with cyclodextrins, due to their lack of release from the complex. γ-Cyclodextrin is digestible in contrast to β-cyclodextrins. This could potentially limit the sensitivity toward overdose, which was evaluated using benzo[a]pyrene in this study, in which rats were administered benzo[a]pyrene and different doses of the 2 cyclodextrins. Both cyclodextrins lowered the area under the curve and therefore the absorption of benzo[a]pyrene by up to a factor of 2 when dosed in high concentrations, thus indicating that overdosing of cyclodextrins may limit the oral absorption of a compound. This limitation may be artificial because the molar ratio of benzo[a]pyrene:cyclodextrin was >1:50,000 at the concentration where a significant decrease in the absorption was observed. No difference was observed between the 2 cyclodextrins, so digestibility seemed less important. More interesting was that the decrease in absorption was relatively small when compared with literature values, suggesting that the effect of overdosing a compound with cyclodextrins was lower than anticipated.
authors.affiliation: Pharmaceutical Science and CMC Biologics, H. Lundbeck A/S, Valby, Denmark; NSM, Research Unit for Functional Biomaterials, Roskilde University, Roskilde, Denmark.
authors.forename: Niels E
authors.initials: NE
authors.lastname: Olesen
authors.affiliation: Pharmaceutical Science and CMC Biologics, H. Lundbeck A/S, Valby, Denmark; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Vana
authors.affiliation: Pharmaceutical Science and CMC Biologics, H. Lundbeck A/S, Valby, Denmark. Electronic address: rhol@lundbeck.com.
authors.forename: René
authors.initials: R
authors.lastname: Holm
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D003505:Cyclodextrins / Q000737:chemistry / Q000378:metabolism*; D004339:Drug Compounding; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D047408:gamma-Cyclodextrins / Q000737:chemistry / Q000378:metabolism
chemical_list: D003505:Cyclodextrins; D047408:gamma-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001564:Benzo(a)pyrene
keywords: benzo[a]pyrene; bile; cyclodextrins; hydroxypropyl-β-cyclodextrin; rats; stability constants; γ-cyclodextrins