Pharmacokinetic interaction between oltipraz and silymarin in rats.
OBJECTIVE
To evaluate the pharmacokinetic interaction between oltipraz and silymarin after intravenous and oral administration of both drugs to male Sprague-Dawley rats.


METHODS
Oltipraz (single doses of 10 and 30 mg/kg for intravenous and oral administration, respectively), silymarin (single doses of 50 and 100 mg/kg for intravenous and oral administration, respectively, and 14 days oral administration of 100 mg/kg), alone and together were administered to control rats.


RESULTS
The pharmacokinetic parameters of oltipraz did not significantly altered by silymarin. However, after intravenous administration of the drugs together, the AUCs of unconjugated, conjugated, and total (unconjugated plus conjugated) silibinin were significantly different (32.7% decrease, and 32.1% and 27.2% increase, respectively), and total and (CL) and non-renal (CL NR ) clearance of unconjugated silibinin were significantly faster (49.4% and 61.1% increase, respectively) than those of silymarin alone (without oltipraz). After oral administration of silymarin with or without oltipraz, however, the pharmacokinetic parameters of unconjugated, conjugated, and total silibinin were comparable.


CONCLUSIONS
After single intravenous administration of the drugs together, the AUC of unconjugated silibinin was significantly smaller, but that of both conjugated and total silibinin was significantly greater. This could have been due to an increase in the formation of conjugates (glucuronidation and sulfation) of silibinin as induced by oltipraz. After simultaneous oral administration of the drugs, however, the AUCs (or AUC 0-12 h) of unconjugated, conjugated, and total silibinin were comparable.
Kang
Min Kyung
MK
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Bae
Soo Kyung
SK
Kim
Jin Wan
JW
Lee
Myung Gull
MG
D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents; D019540:Area Under Curve; D004347:Drug Interactions; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000378:metabolism; D011719:Pyrazines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013871:Thiones; D013876:Thiophenes; D014018:Tissue Distribution
D016588:Anticarcinogenic Agents; D011719:Pyrazines; D012838:Silymarin; D013871:Thiones; D013876:Thiophenes; D000077385:Silybin; C026209:oltipraz