Effect of inhalation exposure to toluene on the activity of organic anion transporting polypeptide (Oatp) using pravastatin as a probe drug in rats

• Published in: Xenobiotica 2018-07, Vol.48 (7), p.734-738
• Main Authors: Mauro, Mariana, Lepera, Jose Salvador, Borsari, Bruno, Capela, Jorge Manuel Vieira, de Moraes, Natália Valadares
• Format: Article
• Language: English
• Subjects: Animals; Inhalation Exposure; Kinetics; Male; Molecular Probes - pharmacology; Organic Anion Transporters - metabolism; Pravastatin - blood; Pravastatin - pharmacokinetics; Pravastatin - pharmacology; Rats, Wistar; Time Factors; Toluene - toxicity
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/00498254.2017.1353717

1. Toluene, used as a pure substance or in solvent mixtures, is the cause of occupational exposures of large numbers of workers in the world. The organic anion transporting polypeptides (OATP: human; Oatp: rodents) are drug carriers which have been frequently associated to drug-drug interactions. The objective of this study was to evaluate the influence of inhalation exposure to toluene in Oatp in vivo activity using pravastatin as a probe drug in rats. 2. Male Wistar rats ((n = 6 per sampling time) were exposed to 85 mg/m toluene by inhalation or air in a nose only exposure system for 6 h/d, 5 d/week during 4 weeks, in order to simulate the occupational exposure to toluene at level slightly above the occupational exposure limit proposed by the American Conference of Governmental Industrial Hygienists (ACGIH). After 4 weeks of exposure, animals received a single dose of 20 mg/kg pravastatin orally. 3. Areas under concentration × time curves extrapolated to infinite (AUC ) were calculated by Gauss Laguerre quadrature. Non-exposed animals showed AUC of 726.0 (261.8) ng h/mL for pravastatin and rats exposed to toluene 85 mg/m3 showed AUC of 681.8 (80.1) ng h/mL [data presented as mean (standard error of the mean)]. No significant difference was observed in pravastatin kinetic disposition between groups in terms of 95% confidence interval for the difference between means. 4. Toluene exposure by inhalation did not change the in vivo activity of Oatp evaluated by pravastatin kinetic disposition in rats.