RT Journal Article
SR Electronic
T1 Use of Online Microdialysis Sampling to Determine the in Vivo Rate of Phenol Glucuronidation in Rainbow Trout
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1406
OP 1413
DO 10.1124/dmd.107.020123
VO 36
IS 7
A1 John W. Nichols
A1 Alex D. Hoffman
A1 Patrick N. Fitzsimmons
A1 Gregory J. Lien
A1 Correne T. Jenson
YR 2008
UL http://dmd.aspetjournals.org/content/36/7/1406.abstract
AB A quantitative microdialysis (MD) sampling method was used to study phenol (PH) glucuronidation in vivo in rainbow trout. The method employs internal calibrators to account for changes in MD probe performance (in vitro-to-in vivo and sample-to-sample) and yields data of high temporal resolution that are well suited for developing kinetic models. Initially, trout were dosed with phenyl glucuronide (PG) by intravascular infusion for 24 h and then depurated for 48 h. Measured concentrations of PG in blood were well described by a one-compartment clearance-volume model. Massbalance calculations showed that 93% of infused PG was eliminated in urine during the depuration period. Peak concentrations of PG in urine averaged 3.4 times higher than those in blood, and the fitted PG clearance constant (15.7 ml/kg/h) was about 2.6 times higher than the reported glomerular filtration rate for trout. These findings confirm earlier work suggesting that PG is actively secreted by the trout kidney. In a second set of experiments, trout were exposed continuously to PH in water. In vivo rate constants for PH glucuronidation were estimated using a pair of linked (PH and PG) one-compartment clearance-volume models. Expressed on a whole-fish basis, the glucuronidation rate averaged 0.049/h, which was about 7% of the total rate of PH elimination. This study demonstrates the utility of quantitative MD sampling for kinetic studies of xenobiotic metabolism in fish. The American Society for Pharmacology and Experimental Therapeutics