Abstract
The objective of this work was to assess the influence of binding to plasma proteins and to serum on the brain extraction of four antiinflammatory oxicams. The brain extraction of isoxicam, tenoxicam, meloxicam and piroxicam was investigated in rats using the carotid injection technique. Blood protein binding parameters were determined by equilibrium dialysis using human serum, human serum albumin (HSA) and alpha-l-acid glycoprotein (AAG) solutions at various concentrations. All oxicams had low values of brain extraction, between 19% and 39% when dissolved in serum, i.e. under physiological conditions. Brain efflux rate constants calculated from the wash-out curves were the same in the absence or presence of serum. Brain efflux was inversely related to the polarity of the oxicams, such that the higher their H-bonding capacity, the lower their brain efflux. The free dialyzable drug fraction was inversely related to protein concentration. However, rat brain extraction was always higher than expected from in vitro measurements of the dialyzable fraction. Except for piroxicam whose brain extraction was partially decreased in the presence of proteins, the serum unbound and initially bound fractions of oxicams both seem available for...Continue Reading
Citations
Apr 20, 2012·European Journal of Anaesthesiology·Angela R KamerAlex Bekker
Feb 26, 2013·Fluids and Barriers of the CNS·Elizabeth Cm de Lange
Feb 22, 2016·BMC Veterinary Research·Umit KarademirCengiz Gokbulut
Jan 1, 2015·Journal of Microscopy and Ultrastructure·Amany M Mousa, Amal A Shehab
Feb 23, 1999·Fundamental & Clinical Pharmacology·P Jolliet-Riant, J P Tillement
Aug 23, 2008·Anesthesiology·Shailendra JoshiEugene Ornstein
Nov 20, 2012·Journal of the American Society of Nephrology : JASN·Emma T B Olesen, Robert A Fenton
Jan 28, 2014·PloS One·Iveta NovakovaWinfried Neuhaus
Sep 5, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ana P CostaNicolas F Villarino
Jun 19, 2007·Neurocritical Care·Shailendra JoshiJeffrey N Bruce
Mar 7, 2020·Molecular Biology Reports·Karolina Wanat
Aug 7, 2002·Clinical Pharmacokinetics·Elizabeth C M de Lange, Meindert Danhof
Nov 30, 2005·Journal of Biomolecular Screening·Chi Ho YoonSun Dong Yoo
Dec 16, 2005·The AAPS Journal·Elizabeth C M de LangeTamara J van Steeg
Mar 22, 2014·Pharmaceutics·Raj K Singh BadhanJeffrey I Penny
Feb 20, 2002·Chemical Reviews·Alessandra PagliaraBernard Testa
Dec 25, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Katarzyna CzaplaEwa Rogalska
Apr 2, 2003·European Journal of Medicinal Chemistry·Li DiGuy T Carter
Aug 9, 2005·Journal of Pharmaceutical and Biomedical Analysis·Neelam Seedher, Sonu Bhatia
Jul 5, 2005·Pharmacology & Therapeutics·Maria Burian, Gerd Geisslinger
Apr 4, 1998·Journal of Medicinal Chemistry·A PagliaraJ P Rihoux
Aug 16, 2018·Molecular Pharmaceutics·Huan LiJunqing Yang
Jul 23, 2004·Journal of Medicinal Chemistry·Giuseppe ErmondiGiulia Caron
Jan 22, 2010·Journal of Pharmaceutical and Biomedical Analysis·Lilianna Trynda-Lemiesz, Katarzyna Wiglusz