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Titolo:
Mathematical modelling of the chemotherapy of Plasmodium falciparum malaria with artesunate: postulation of 'dormancy', a partial cytostatic effect of the drug, and its implication for treatment regimens
Autore:
Hoshen, MB; Na-Bangchang, K; Stein, WD; Ginsburg, H;
Indirizzi:
Hebrew Univ Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91904 -91904 Jerusalem, Israel Mahidol Univ, Fac Trop Med, Clin Pharmacol Unit, Bangkok, Thailand MahidolUniv Bangkok Thailand d, Clin Pharmacol Unit, Bangkok, Thailand
Titolo Testata:
PARASITOLOGY
, volume: 121, anno: 2000,
parte:, 3
pagine: 237 - 246
SICI:
0031-1820(200009)121:<237:MMOTCO>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOSE ARTEMISININ-MEFLOQUINE; IN-VIVO PHARMACOKINETICS; ORAL ARTESUNATE; ANTIMALARIAL-DRUGS; PHARMACODYNAMIC PROPERTIES; COMBINATION; EFFICACY; ARTEMETHER; RESISTANCE; CHILDREN;
Keywords:
Plasmodium falciparum malaria; artesunate; mathematical model; pharmacokinetics; pharmacodynamics; dormancy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Ginsburg, H Hebrew Univ Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91904Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91904 alem, Israel
Citazione:
M.B. Hoshen et al., "Mathematical modelling of the chemotherapy of Plasmodium falciparum malaria with artesunate: postulation of 'dormancy', a partial cytostatic effect of the drug, and its implication for treatment regimens", PARASITOL, 121, 2000, pp. 237-246

Abstract

Although artesunate, one of the potent derivatives of the qinghaosu familyof drugs for treating falciparum malaria, is already in use in the field, its therapeutic protocol has only been developed empirically by hit-or-miss. A pharmacokinetic-pharmacodynamic (PK-PD) model, required for creating such a protocol, is nor straightforward. Artesunate presents extremely fast pharmacokinetics. As a result the stage specificity of its action must be treated explicitly. Also, use of standard PK-PD modelling fails to explain the clinical results. Our PK-PD modelling of its activity leads us to the postulation of the existence of a novel effect: a small fraction of the parasites, as a result of chemotherapeutic pressure, become cytostatic, or 'dormant'. At this stage, the parasite cycle is halted, making them unsusceptibleto further dosing until wakening. This slows down the antimalarial activity of the drug, entailing either many frequent doses or an extended period of treatment and surveillance. Based on our modelling, we suggest a method for deciding on rational models of chemotherapy against falciparum malaria.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 22:04:53