Dog model with implanted pump to test boosters for antiretroviral medication

التفاصيل البيبلوغرافية
العنوان: Dog model with implanted pump to test boosters for antiretroviral medication
المؤلفون: Sophie Lachau-Durand, Piet Wigerinck, Laurent Schueller, Ellen Clessens, Guy Van den Mooter, Lieven Baert, Herman Borghys, Jan Rosier, Tim Hugo Maria Jonckers, Elke Van Gyseghem, Pieter Van Remoortere
المصدر: International Journal of Pharmaceutics. 355:45-52
بيانات النشر: Elsevier BV, 2008.
سنة النشر: 2008
مصطلحات موضوعية: Male, medicine.medical_specialty, Anti-HIV Agents, Cmax, Pharmaceutical Science, complex mixtures, Dogs, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, medicine, Animals, Infusion pump, Darunavir, Sulfonamides, Ritonavir, business.industry, Area under the curve, Drug Synergism, HIV Protease Inhibitors, Infusion Pumps, Implantable, Venous blood, Surgery, Data Interpretation, Statistical, Anesthesia, Antiretroviral medication, business, medicine.drug, Blood sampling
الوصف: 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 25 mg/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 40 mg/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.
تدمد: 0378-5173
DOI: 10.1016/j.ijpharm.2007.09.025
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9fc2c946cb3bd87fe4221ede6120d07
https://doi.org/10.1016/j.ijpharm.2007.09.025
Rights: CLOSED
رقم الانضمام: edsair.doi.dedup.....e9fc2c946cb3bd87fe4221ede6120d07
قاعدة البيانات: OpenAIRE
الوصف
تدمد:03785173
DOI:10.1016/j.ijpharm.2007.09.025