PMID- 12898182
OWN - NLM
STAT- MEDLINE
DCOM- 20031203
LR  - 20061115
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 52
IP  - 5
DP  - 2003 Nov
TI  - Bioavailability and pharmacokinetics of the cardioprotecting flavonoid 
      7-monohydroxyethylrutoside in mice.
PG  - 371-6
AB  - PURPOSE: The pharmacokinetics and bioavailability of monoHER, a promising 
      protector against doxorubicin-induced cardiotoxicity, were determined after 
      different routes of administration. METHODS: Mice were treated with 500 mg.kg(-1) 
      monoHER intraperitoneally (i.p.), subcutaneously (s.c.) or intravenously (i.v.) 
      or with 1000 mg.kg(-1) orally. Heart tissue and plasma were collected 24 h after 
      administration. In addition liver and kidney tissues were collected after s.c. 
      administration. The levels of monoHER were measured by HPLC with electrochemical 
      detection. RESULTS: After i.v. administration the AUC(0-120 min) values of 
      monoHER in plasma and heart tissue were 20.5+/-5.3 micromol.min.ml(-1) and 
      4.9+/-1.3 micromol.min.g(-1) wet tissue, respectively. After i.p. administration, 
      a mean peak plasma concentration of about 130 microM monoHER was maintained from 
      5 to 15 min after administration. The AUC(0-120 min) values of monoHER were 
      6.1+/-1.1 micromol.min.ml(-1) and 1.6+/-0.4 micromol.min.g(-1) wet tissue in 
      plasma and heart tissue, respectively. After s.c. administration, monoHER levels 
      in plasma reached a maximum (about 230 microM) between 10 and 20 min after 
      administration. The AUC(0-120 min) values of monoHER in plasma, heart, liver and 
      kidney tissues were 8.0+/-0.6 micromol.min.ml(-1), 2.0+/-0.1, 22.4+/-2.0 and 
      20.5+/-5.7 micromol.min.g(-1), respectively. The i.p. and s.c. bioavailabilities 
      were about 30% and 40%, respectively. After oral administration, monoHER could 
      not be detected in plasma, indicating that monoHER had a very poor oral 
      bioavailability. CONCLUSIONS: MonoHER was amply taken up by the drug elimination 
      organs liver and kidney and less by the target organ heart. Under 
      cardioprotective conditions (500 mg/kg, i.p.), the Cmax was 131 microM and the 
      AUC(infinity) was 6.3 microM.min. These values will be considered endpoints for 
      the clinical phase I study of monoHER.
FAU - Abou El Hassan, Mohamed A I
AU  - Abou El Hassan MA
AD  - Clinical Research Laboratory of Medical Oncology, Department of Medical Oncology, 
      Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The 
      Netherlands.
FAU - Kedde, Marc A
AU  - Kedde MA
FAU - Zwiers, Ursula T H
AU  - Zwiers UT
FAU - Tourn, E
AU  - Tourn E
FAU - Haenen, Guido R M M
AU  - Haenen GR
FAU - Bast, Aalt
AU  - Bast A
FAU - van der Vijgh, Wim J F
AU  - van der Vijgh WJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20030731
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Hydroxyethylrutoside)
SB  - IM
MH  - Administration, Oral
MH  - Algorithms
MH  - Animals
MH  - Area Under Curve
MH  - Biological Availability
MH  - Biotransformation
MH  - Chromatography, High Pressure Liquid
MH  - Hydroxyethylrutoside/administration & dosage/blood/*pharmacokinetics
MH  - Injections, Intraperitoneal
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Kidney/metabolism
MH  - Liver/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Myocardium/metabolism
EDAT- 2003/08/05 05:00
MHDA- 2003/12/04 05:00
CRDT- 2003/08/05 05:00
PHST- 2002/12/20 00:00 [received]
PHST- 2003/05/07 00:00 [accepted]
PHST- 2003/08/05 05:00 [pubmed]
PHST- 2003/12/04 05:00 [medline]
PHST- 2003/08/05 05:00 [entrez]
AID - 10.1007/s00280-003-0667-z [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2003 Nov;52(5):371-6. doi: 10.1007/s00280-003-0667-z. 
      Epub 2003 Jul 31.