@article { WOS:000684111200002,
	title = {Enhancement of Docetaxel Absorption Using Ritonavir in an Oral Milk-Based Formulation},
	journal = {PHARMACEUTICAL RESEARCH},
	volume = {38},
	number = {8},
	year = {2021},
	month = {AUG},
	pages = {1419-1428},
	publisher = {SPRINGER/PLENUM PUBLISHERS},
	type = {Article},
	address = {233 SPRING ST, NEW YORK, NY 10013 USA},
	abstract = {Objective The current study aimed to develop a novel milk-based formulation of docetaxel, a sparingly soluble antineoplastic agent, administered so far exclusively by the intravenous route and evaluate its oral bioavailability. Methods Pre-formulation studies included the determination of docetaxel solubility in water-alcohol mixtures as well as short-term content uniformity experiments of the final formulation. The pharmacokinetic (PK) performance of the developed milk-based formulations was further evaluated in vivo in mice using ritonavir, a potent P-glycoprotein inhibitor, as an absorption enhancer of docetaxel and the marketed intravenous docetaxel formulation, Taxotere (R), as a control. Results In vivo PK results in mice showed that all the administered oral docetaxel formulations had limited absorption in the absence of ritonavir. On the contrary, ritonavir co-administration given as pre-treatment significantly enhanced oral bioavailability of both the marketed and milk-based docetaxel formulations; an even more marked increase in drug exposure was observed when ritonavir was incorporated within the docetaxel milk-based formulation. The fixed-dose combination also showed a more prolonged absorption of the drug compared to separate administrations. Conclusions The current study provides insights for the discovery of a novel milk-based formulation that could potentially serve as an alternative, non-toxic and patient-friendly carrier for an acceptable docetaxel oral chemotherapy.},
	keywords = {Docetaxel, milk-based formulation, oral bioavailability, Ritonavir},
	issn = {0724-8741},
	doi = {10.1007/s11095-021-03085-x},
	author = {Soulele, K. and Karampelas, T. and Tamvakopoulos, C. and Macheras, P.}
}
