title: Evaluation on activity of cytochrome p450 enzymes in turbot via a probe drug cocktail.
abstract: Cytochrome P450s (CYPs) are the main catalytic enzymes for metabolism by a variety of endogenous and exogenous substrates in mammals, fish, insects, etc. We evaluated the application of a multidrug cocktail on changes in CYP1, CYP2, and CYP3 activity in Turbot Scophthalmus maximus. The probe drugs were a combination of caffeine (5 mg/kg body weight), dapsone (5 mg/kg), and chlorzoxazone (10 mg/kg). After a single intraperitoneal injection of the cocktail, the concentration of all three probe drugs in the plasma increased quickly to a peak and then decreased gradually over 24 h. Pharmacokinetic profiles of the three probe drugs were determined using a noncompartmental analysis, and the typical parameters were calculated. In the assay for CYP induction, pretreatment with rifampicin significantly reduced the typical pharmacokinetic metrics for caffeine and chlorzoxazone, but not dapsone, indicating that the activity of CYP1 and CYP2 in turbot were induced by rifampicin.
authors.affiliation: a Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences , 106 Nanjing Road, Qingdao 266071 , China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Chang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Zhai
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D002110:Caffeine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D002753:Chlorzoxazone / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D003622:Dapsone / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D004790:Enzyme Induction / Q000187:drug effects; D005412:Flatfishes / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D009125:Muscle Relaxants, Central / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D012293:Rifampin / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D005493:Folic Acid Antagonists; D009125:Muscle Relaxants, Central; D019384:Nucleic Acid Synthesis Inhibitors; D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D003622:Dapsone; D003577:Cytochrome P-450 Enzyme System; D002753:Chlorzoxazone; D012293:Rifampin