Title: Dog model with implanted pump to test boosters for antiretroviral medication
Authors: Schueller, Laurent ×
Baert, Lieven
Lachau-Durand, Sophie
Borghys, Herman
Clessens, Ellen
Van den Mooter, Guy
Van Gyseghem, Elke
Jonckers, Tim H M
Van Remoortere, Pieter
Wigerinck, Piet
Rosier, Jan #
Issue Date: May-2008
Publisher: Elsevier/North Holland
Series Title: International Journal of Pharmaceutics vol:355 issue:1-2 pages:45-52
Abstract: A dog model was developed to test the capacity of boosters for antiretroviral medication. Two dogs were implanted with a modified constant-flow Codman 3000 infusion pump, adapted to release viscous solutions of darunavir (TMC114) at a constant rate of 25mg/dog/day in the venous blood stream. Booster candidates were given by oral gavage for at least 4 days up to maximum 7 days in cross-over fashion, separated by a wash-out period of minimum 1 week. The booster candidates were tested at doses of 20 and/or 40mg/kg/day: blood sampling for determination of the boosting effect was performed on the last day of booster administration. The model allowed to (1) compare the boosting ratio of these booster candidates based on the exposure (determination of the area under the curve (AUC) of darunavir in presence versus absence of the booster candidate), (2) detect delay in boosting activity by evaluation of the shift of Cmax of darunavir following booster administration versus the Cmax of the booster candidate) and (3) calculate the intrinsic booster capacity, by correcting for the systemic exposure of booster candidate by normalizing the booster ratio for the booster's AUC. The latter parameter (intrinsic booster capacity) allows to determine the booster's metabolic contribution in inhibiting the metabolism of antiretroviral medication (most likely via inhibition of CYP3A4), minimizing the impact of potential effects of the booster at the level of the gastro-intestinal tract.
ISSN: 0378-5173
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Faculty of Pharmaceutical Sciences - miscellaneous
Drug Delivery and Disposition
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
2008-Schueller-Dog model with implanted.pdf Published 467KbAdobe PDFView/Open Request a copy

These files are only available to some KU Leuven Association staff members


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science