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Titolo:
A difference between the rat and mouse in the pharmacokinetic interaction of 5,6-dimethylxanthenone-4-acetic acid with thalidomide
Autore:
Zhou, SF; Kestell, P; Tingle, MD; Ching, LM; Paxton, JW;
Indirizzi:
Univ Auckland, Dept Pharmacol & Clin Pharmacol, Auckland 1, New Zealand Univ Auckland Auckland New Zealand 1 Pharmacol, Auckland 1, New Zealand Univ Auckland, Auckland Canc Soc, Res Inst, Auckland 1, New Zealand Univ Auckland Auckland New Zealand 1 , Res Inst, Auckland 1, New Zealand
Titolo Testata:
CANCER CHEMOTHERAPY AND PHARMACOLOGY
fascicolo: 6, volume: 47, anno: 2001,
pagine: 541 - 544
SICI:
0344-5704(200106)47:6<541:ADBTRA>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTICANCER DRUG; NITRIC-OXIDE; METABOLISM; CYTOCHROME-P-450; ACTIVATION; MICROSOMES; CYTOKINES; ALPHA;
Keywords:
cyproheptadine; diclofenac; DMXAA; thalidomide; drug interaction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Paxton, JW Univ Auckland, Dept Pharmacol & Clin Pharmacol, Private Bag 92019, Auckland 1, New Zealand Univ Auckland Private Bag 92019 Auckland New Zealand 1 Zealand
Citazione:
S.F. Zhou et al., "A difference between the rat and mouse in the pharmacokinetic interaction of 5,6-dimethylxanthenone-4-acetic acid with thalidomide", CANC CHEMOT, 47(6), 2001, pp. 541-544

Abstract

Purpose: Coadministration of thalidomide, cyproheptadine or diclofenac hasbeen shown to increase the area under the plasma concentration-time curve (AUC) of the novel antitumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) ill mice. The aim of this study was to further investigate these pharmacokinetic DMXAA-drug interactions in the rat model. Methods: The effects of coadministration of L-thalidomide, cyproheptadine or diclofenac on the pharmacokinetics of DMXAA were investigated in male Wistar Kyoto rats. The effects of L-thalidomide, cyproheptadine and diclofenac on microsomal metabolism and plasma protein binding of DMXAA were also investigated. Results. No significant alteration in the plasma concentration profile for DMXAA was observed following L-thalidomide pretreatment in rats. In contrast, when combined with diclofenac or cyproheptadine, the plasma AUC of DMXAA was significantly (P < 0.05) increased by 48% and 88% and the T-1/2 by 36% and 107%,respectively, compared to controls. Both diclofenac and cyproheptadine at 500 muM caused a significant inhibition of DMXAA metabolism in rat liver microsomes. In contrast, L-thalidomide had no or little inhibitory effect on DMXAA metabolism in rat liver microsomes except for causing a 32% decrease in 6-methylhydroxylation at 500 muM. None of the drugs had a significant effect on the plasma protein binding of DMXAA in the rat. Conclusion. These studies showed that coadministration of L-thalidomide did not alter the plasma DMXAA AUC in rats, in contrast to previous studies in mice, whereas diclofenac and cyproheptadine significantly reduced the plasma clearance of DMXAA in rats in a similar manner to their effect in mice. The cause of the species difference in the pharmacokinetic response to thalidomide by DMXAA isunknown, and indicates difficulties in predicting the outcome of such a combination in patients.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 08:30:35