RT Journal Article
SR Electronic
T1 Control and Measurement of Plasma pH in Equilibrium Dialysis: Influence on Drug Plasma Protein Binding
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 551
OP 557
DO 10.1124/dmd.110.036988
VO 39
IS 3
A1 Ruth E. Curran
A1 Christopher R. J. Claxton
A1 Laura Hutchison
A1 Paul J. Harradine
A1 Iain J. Martin
A1 Peter Littlewood
YR 2011
UL http://dmd.aspetjournals.org/content/39/3/551.abstract
AB Past publications have highlighted the influence of postdialysis plasma pH on the measured fraction unbound in plasma (fup). There is disparity in the industry as to which of two main methods is more suitable for controlling postdialysis plasma pH: the use of either a stronger buffer or a CO2 atmosphere for the incubation. In the current study, it has been found that 10% CO2 could be too high for the buffering capacities of both 100 mM sodium phosphate (pH 7.40 decreased to pH 6.90 after a 6-h incubation) and plasma (decreased below pH 7.40 after a 6-h incubation). To provide appropriate control over the postdialysis plasma pH, for a range of species, it is proposed that a standard phosphate buffer strength (100 mM) and pH (7.40) in combination with a 5% CO2 atmosphere be used for equilibrium dialysis. Furthermore, statistically significant differences in fup values obtained with a pH difference of less than 0.32 pH unit have been demonstrated. An acceptance range for postdialysis plasma pH in routine in vitro fup screening assays of pH 7.40 ± 0.10 is recommended.