In vivo effects of naproxen, salicylic acid, and valproic acid on the pharmacokinetics of trichloroethylene and metabolites in rats.
J Toxicol Environ Health A
; 78(11): 671-84, 2015.
Article
in En
| MEDLINE
| ID: mdl-26039745
ABSTRACT
It was recently demonstrated that some drugs modulate in vitro metabolism of trichloroethylene (TCE) in humans and rats. The objective was to assess in vivo interactions between TCE and three drugs naproxen (NA), valproic acid (VA), and salicylic acid (SA). Animals were exposed to TCE by inhalation (50 ppm for 6 h) and administered a bolus dose of drug by gavage, equivalent to 10-fold greater than the recommended daily dose. Samples of blood, urine, and collected tissues were analyzed by headspace gas chromatography coupled to an electron capture detector for TCE and metabolites (trichloroethanol [TCOH] and trichloroacetate [TCA]) levels. Coexposure to NA and TCE significantly increased (up to 50%) total and free TCOH (TCOHtotal and TCOHfree, respectively) in blood. This modulation may be explained by an inhibition of glucuronidation. VA significantly elevated TCE levels in blood (up to 50%) with a marked effect on TCOHtotal excretion in urine but not in blood. In contrast, SA produced an increase in TCOHtotal levels in blood at 30, 60, and 90 min and urine after coexposure. Data confirm in vitro observations that NA, VA, and SA affect in vivo TCE kinetics. Future efforts need to be directed to evaluate whether populations chronically medicated with the considered drugs display greater health risks related to TCE exposure.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Solvents
/
Trichloroacetic Acid
/
Trichloroethylene
/
Naproxen
/
Valproic Acid
/
Salicylic Acid
/
Ethylene Chlorohydrin
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
J Toxicol Environ Health A
Journal subject:
SAUDE AMBIENTAL
/
TOXICOLOGIA
Year:
2015
Document type:
Article
Affiliation country:
Canada
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM