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Bioavailability and pharmacokinetics of the cardioprotecting flavonoid 7-monohydroxyethylrutoside in mice.
Cancer Chemother Pharmacol 2003; 52(5):371-6CC

Abstract

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.

Authors+Show Affiliations

Clinical Research Laboratory of Medical Oncology, Department of Medical Oncology, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

12898182

Citation

Abou El Hassan, Mohamed A I., et al. "Bioavailability and Pharmacokinetics of the Cardioprotecting Flavonoid 7-monohydroxyethylrutoside in Mice." Cancer Chemotherapy and Pharmacology, vol. 52, no. 5, 2003, pp. 371-6.
Abou El Hassan MA, Kedde MA, Zwiers UT, et al. Bioavailability and pharmacokinetics of the cardioprotecting flavonoid 7-monohydroxyethylrutoside in mice. Cancer Chemother Pharmacol. 2003;52(5):371-6.
Abou El Hassan, M. A., Kedde, M. A., Zwiers, U. T., Tourn, E., Haenen, G. R., Bast, A., & van der Vijgh, W. J. (2003). Bioavailability and pharmacokinetics of the cardioprotecting flavonoid 7-monohydroxyethylrutoside in mice. Cancer Chemotherapy and Pharmacology, 52(5), pp. 371-6.
Abou El Hassan MA, et al. Bioavailability and Pharmacokinetics of the Cardioprotecting Flavonoid 7-monohydroxyethylrutoside in Mice. Cancer Chemother Pharmacol. 2003;52(5):371-6. PubMed PMID: 12898182.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bioavailability and pharmacokinetics of the cardioprotecting flavonoid 7-monohydroxyethylrutoside in mice. AU - Abou El Hassan,Mohamed A I, AU - Kedde,Marc A, AU - Zwiers,Ursula T H, AU - Tourn,E, AU - Haenen,Guido R M M, AU - Bast,Aalt, AU - van der Vijgh,Wim J F, Y1 - 2003/07/31/ PY - 2002/12/20/received PY - 2003/05/07/accepted PY - 2003/8/5/pubmed PY - 2003/12/4/medline PY - 2003/8/5/entrez SP - 371 EP - 6 JF - Cancer chemotherapy and pharmacology JO - Cancer Chemother. Pharmacol. VL - 52 IS - 5 N2 - 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. SN - 0344-5704 UR - https://www.unboundmedicine.com/medline/citation/12898182/Bioavailability_and_pharmacokinetics_of_the_cardioprotecting_flavonoid_7_monohydroxyethylrutoside_in_mice_ L2 - https://dx.doi.org/10.1007/s00280-003-0667-z DB - PRIME DP - Unbound Medicine ER -