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.

Pharmacokinetics of [14C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction

“…Not unexpectedly, the C max ratio was also about 7 orders of magnitude different (233 ng/mL versus 70 fg/mL). Pharmacokinetic studies in the rat indicate a much longer time for absorption with a T max of 5–8 hours (Olesen et al, 2016; Ramesh et al, 2001). The Olesen et al (2016) study dosed male Sprague-Dawley rats (fasted overnight and for 8 hours post-dosing) with 1.05 µg/kg b.w [ 3 H]-BaP by oral gavage in ethanol whereas the Ramesh et al (2001) study dosed male Fisher-344 rats (fasted for 16 hours prior to dosing) with 100 mg/kg b.w.…”