Pharmacokinetic interaction between oltipraz and dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) after single intravenous and oral administration to rats.
The aim of this study was to report the pharmacokinetic interaction between oltipraz (50 mg kg(-1)) and dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB, 10 mg kg(-1)) after single intravenous and oral administration to rats. After intravenous administration of oltipraz plus DDB, the area under the plasma concentration-time curve from time zero to time infinity (AUC) of oltipraz was significantly greater (1440 vs 1740 microg min mL(-1)) than that after oltipraz alone. This was not due to slower clearances of oltipraz after oltipraz plus DDB since the total body, renal and nonrenal clearances were comparable between the two groups of rats. It could be due to a decrease in tissue binding of oltipraz by DDB. The apparent volume of distribution at steady state (Vd(ss)) of DDB was significantly smaller (7060 vs 4650 mL kg(-1)) than after oltipraz alone. After oral administration of oltipraz plus DDB, the AUC of olitpraz was also significantly greater (479 vs 583 microg min mL(-1)) than that after oltipraz alone. This was not due to increased absorption of oltipraz from the rat gastrointestinal tract after oltipraz plus DDB but again could be due to a decrease in Vd(ss) of oltipraz by DDB. However, after both intravenous and oral administration, the pharmacokinetic parameters of DDB were comparable between DDB alone and DDB plus oltipraz, indicating that oltipraz did not greatly affect the pharmacokinetics of DDB in rats.
Bae
Soo Kyung
SK
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Kwanak-Gu, Korea.
Kim
Eun Jung
EJ
Chung
Suk Jae
SJ
Kim
Sang Geon
SG
Lee
Myung Gull
MG
D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003998:Dicarboxylic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004347:Drug Interactions; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D020011:Protective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011719:Pyrazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013871:Thiones; D013876:Thiophenes; D014018:Tissue Distribution
D016588:Anticarcinogenic Agents; D001713:Biphenyl Compounds; D003998:Dicarboxylic Acids; D020011:Protective Agents; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; C510843:dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate; C026209:oltipraz