The cardioprotector monoHER does not interfere with the pharmacokinetics or the metabolism of the cardiotoxic agent doxorubicin in mice.
OBJECTIVE
Monohydroxyethylrutoside (monoHER) has proved to be a good protector against doxorubicin-induced cardiotoxicity without interfering with the antitumor effect of doxorubicin. The aim of the present study was to determine whether there is a pharmacokinetic interaction between monoHER and doxorubicin which may be involved in monoHER cardioprotection.


METHODS
Mice were treated with monoHER (500 mg x kg(-1) i.v.) alone, monoHER 5 min after doxorubicin (10 mg x kg(-1) i.v.), doxorubicin alone and doxorubicin 5 min after monoHER. The levels of monoHER and doxorubicin(ol) in plasma and heart tissue were measured by HPLC 24 h and 48 h after monoHER and doxorubicin administration, respectively.


RESULTS
The areas under the concentration-time curves (AUCs) of monoHER and doxorubicin(ol) were not affected by the coadministered drug. No changes were observed in pharmacokinetic parameters such as initial and final half-lives, mean residence time, clearance and volume of distribution of monoHER and doxorubicin(ol) after single or combined administration.


CONCLUSIONS
The cardioprotection of monoHER in mice is not caused by a pharmacokinetic interaction between monoHER and doxorubicin.
Department of Medical Oncology, Clinical Research Laboratory of Medical Oncology, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. m.abulhassan@vumc.nl
Mohamed A I
MA
Abou El Hassan
Marc A
MA
Kedde
Ursula T H
UT
Zwiers
Aalt
A
Bast
Wim J F
WJ
van der Vijgh
D000818:Animals; D019540:Area Under Curve; D002316:Cardiotonic Agents / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006207:Half-Life; D006896:Hydroxyethylrutoside / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism*; D014018:Tissue Distribution
D002316:Cardiotonic Agents; D006896:Hydroxyethylrutoside; D004317:Doxorubicin; C010013:adriamycinol