caa a22 4500 477128033 CHVBK 20180405111655.0 cr unu---uuuuu 170330e19970501xx s 000 0 eng 10.1023/A:1012165414610 doi (NATIONALLICENCE)springer-10.1023/A:1012165414610 Blood-to-Brain Transfer of Various Oxicams: Effects of Plasma Binding on Their Brain Delivery [Elektronische Daten] [Pascale Jolliet, Nicolas Simon, Francoise Brée, Saïk Urien, Alessandra Pagliara, Pierre-Alain Carrupt, Bernard Testa, Jean-Paul Tillement] Purpose. 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. Methods. 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-1-acid glycoprotein (AAG) solutions at various concentrations. Results. 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. Conclusions. 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 transfer into the brain. Modest affinities for AAG rule out any related effect. More surprising is the apparent lack of effect on brain transfer of the high-affinity binding to HSA and serum. The enhanced brain uptake of meloxicam in the presence of AAG could be a result of interactions between this globular protein and the endothelial wall. Plenum Publishing Corporation, 1997 blood-brain barrier nationallicence drug brain transfer nationallicence in vivo brain extraction nationallicence plasma protein binding nationallicence oxicams nationallicence Jolliet Pascale Service de Pharmacologie, Faculté de Médecine PARIS XII, F-, 94010, Créteil, France aut Simon Nicolas Service de Pharmacologie, Faculté de Médecine PARIS XII, F-, 94010, Créteil, France aut Brée Francoise Service de Pharmacologie, Faculté de Médecine PARIS XII, F-, 94010, Créteil, France aut Urien Saïk Service de Pharmacologie, Faculté de Médecine PARIS XII, F-, 94010, Créteil, France aut Pagliara Alessandra Ecole de Pharmacie, Université de Lausanne, CH-, 1015, Lausanne, Switzerland aut Carrupt Pierre-Alain Ecole de Pharmacie, Université de Lausanne, CH-, 1015, Lausanne, Switzerland aut Testa Bernard Ecole de Pharmacie, Université de Lausanne, CH-, 1015, Lausanne, Switzerland aut Tillement Jean-Paul Service de Pharmacologie, Faculté de Médecine PARIS XII, F-, 94010, Créteil, France aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 650-656 0724-8741 14:5<650 1997 14 11095 https://doi.org/10.1023/A:1012165414610 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012165414610 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jolliet Pascale Service de Pharmacologie, Faculté de Médecine PARIS XII, F-, 94010, Créteil, France aut NATIONALLICENCE 700 1- Simon Nicolas Service de Pharmacologie, Faculté de Médecine PARIS XII, F-, 94010, Créteil, France aut NATIONALLICENCE 700 1- Brée Francoise Service de Pharmacologie, Faculté de Médecine PARIS XII, F-, 94010, Créteil, France aut NATIONALLICENCE 700 1- Urien Saïk Service de Pharmacologie, Faculté de Médecine PARIS XII, F-, 94010, Créteil, France aut NATIONALLICENCE 700 1- Pagliara Alessandra Ecole de Pharmacie, Université de Lausanne, CH-, 1015, Lausanne, Switzerland aut NATIONALLICENCE 700 1- Carrupt Pierre-Alain Ecole de Pharmacie, Université de Lausanne, CH-, 1015, Lausanne, Switzerland aut NATIONALLICENCE 700 1- Testa Bernard Ecole de Pharmacie, Université de Lausanne, CH-, 1015, Lausanne, Switzerland aut NATIONALLICENCE 700 1- Tillement Jean-Paul Service de Pharmacologie, Faculté de Médecine PARIS XII, F-, 94010, Créteil, France aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 650-656 0724-8741 14:5<650 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer