Pharmacokinetics of tamoxifen after intravenous and oral dosing of tamoxifen-hydroxybutenyl-beta-cyclodextrin formulations.
Oral and intravenous administration of tamoxifen base and tamoxifen citrate formulated with hydroxybutenyl-beta-cyclodextrin (HBenBCD) to Sprague-Dawley rats significantly increased the oral bioavailability of tamoxifen relative to that of parent drug (no HBenBCD). When formulated with HBenBCD, the form of tamoxifen (base vs. salt) made no difference in the oral bioavailability of tamoxifen. Liquid formulations (PG:PEG400:H2O) provided higher oral bioavailability than solid formulations dissolved and dosed as aqueous oral solutions. The oral bioavailability of tamoxifen was significantly influenced by both dietary status and time of dosing of the animals. Tamoxifen metabolite plasma concentrations were not affected by complexation of tamoxifen with HBenBCD. Collectively, the data indicated that dosing of fasted animals in the morning with tamoxifen:HBenBCD formulations provided a very significant increase in tamoxifen oral bioavailability (up to 10- to 14-fold).
Buchanan
Charles M
CM
Eastman Chemical Company, Research Laboratories, P.O. Box 1972, Kingsport, Tennessee 37662, USA. buck@eastman.com
Buchanan
Norma L
NL
Edgar
Kevin J
KJ
Little
James L
JL
Malcolm
Michael O
MO
Ruble
Karen M
KM
Wacher
Vincent J
VJ
Wempe
Michael F
MF
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D047392:beta-Cyclodextrins / Q000008:administration & dosage*
D047392:beta-Cyclodextrins; D013629:Tamoxifen; C031215:betadex