PMID: 9165538May 1, 1997Paper

Blood-to-brain transfer of various oxicams: effects of plasma binding on their brain delivery

Pharmaceutical Research
P JollietJ P Tillement

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 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
Sep 5, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ana P CostaNicolas F Villarino
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
Jan 22, 2010·Journal of Pharmaceutical and Biomedical Analysis·Lilianna Trynda-Lemiesz, Katarzyna Wiglusz

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