Effects of 2-hydroxypropyl-beta-cyclodextrin on pharmacokinetics of digoxin in rabbits and humans.
Considering the narrow therapeutic index of digoxin and the low range between the safe and toxic serum concentrations of this drug, to evaluate the relative bioavailability of tablets and oral solution is necessary. The pharmacokinetic properties of digoxin after oral administration of its hydroxypropyl-beta-cyclodextrin (HPCD) inclusion complex to rabbits and human volunteers were investigated in comparison with those of commercially available tablets. The aqueous solubility of digoxin was enhanced by HPCD for about 2000 times at HPCD concentration of 50% (w/v). But in a human bioavailability study no significant difference was observed in the extent of absorption (AUC(0-t)) and Cmax between the two formulations. Time to reach peak was significantly shorter for the solution than for the tablets (p < 0.01). The pharmacokinetic results from the rabbit study were similar to human studies and no significant difference was observed for AUC, Cmax and Tmax. As the bioavailability of both tablets and solution is equivalent HPCD based oral digoxin solution could serve as an alternative to tablets.
He
Z G
ZG
School of Pharmacy, Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China. hezhgui@mail.sy.ln.cn
Li
Y S
YS
Zhang
T H
TH
Tang
X
X
Zhao
C
C
Zhang
R H
RH
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000293:Adolescent; D000328:Adult; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D003505:Cyclodextrins / Q000494:pharmacology*; D004077:Digoxin / Q000493:pharmacokinetics*; D005079:Excipients; D006801:Humans; D008297:Male; D011817:Rabbits; D012995:Solubility; D012996:Solutions; D013607:Tablets; D013810:Therapeutic Equivalency; D047392:beta-Cyclodextrins
D000889:Anti-Arrhythmia Agents; D003505:Cyclodextrins; D005079:Excipients; D012996:Solutions; D013607:Tablets; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D004077:Digoxin