Preclinical studies with halofantrine
Identifieur interne : 003161 ( Main/Exploration ); précédent : 003160; suivant : 003162Preclinical studies with halofantrine
Auteurs : Brian G. Schuster ; Craig J. CanfieldSource :
- Parasitology Today [ 0169-4758 ] ; 1989.
English descriptors
- Teeft :
- Adverse effect, Anaesthetized mice, Antimalarial, Antimalarial activity, Biochemical changes, Blood cells, Blood pressure, Body weight, Bone marrow, Breast milk, Clinical signs, Clinical studies, Control dams, Desbutyl, Desbutyl halofantrine, Development command contract, Dos, Dose levels, Dosing, Drug administration, Faecal extracts, Falciparum, Falciparum malaria, Female rats, Food consumption, French laboratories, Gestation, Growth rate, Halofantrine, Halofantrine hydrochloride, Heart rate, Higher doses, Hiremath, Immune function, Interim report, Laboratory evidence, Lactation, Maintenance dose, Major component, Malaria, Male mice, Male rats, Mefloquine, Metabolic activation, Mglkg, Minor component, Morphological evidence, Oral administration, Oral doses, Peak concentrations, Peak plasma concentrations, Plasmodium, Plasmodium falciparum, Preclinical, Preclinical trials, Putative metabolite, Radioactive dose, Recovery period, Reproductive performance, Reproductive studies, Research report, Same system, Seminal vesicles, Serum cholesterol, Similar studies, Skeletal anomalies, Skeletal muscle, Smith kline, Study report, Subsequent study, Synthesis report, Target organs, Teratogenic effects, Toxic signs, Toxicity, Twoweek recovery period, Unchanged drug, Unchanged halofantrine, Weight loss.
Abstract
Summary: Habfantrine is one of a series of phenanthrene methanols investigated by WRAIR for us antimalarial activity. It has been shown to be highly active in vitro and to cure malaria in animal models. Its putative metabolite desbutyl halofantrine was shown to be equipotent against chloroquine-resistant and -sensitive P. falciparum strains. At present there is little evidence of cross-resistance between it and other antimalarials in human malaria species.Halofantrine is absorbed to a varying degree by animal species and is widely distributed in tissues. Elimination half-lives vary considerably among species with most of the drug apparently eliminated in the faeces. Significant changes in physiological systems were not observed.Toxicological studies, both acute and sub-acute (28 days), showed effects on a number of target organs at higher doses. No-effect doses were determined to be several times greater than expected human doses considering the systemic exposure to halofantrine. Reproductive studies showed embryotoxic but not teratogenic potential at high doses, and halofantrine was apparently excreted in breast milk. Mutagenicity studies were negative.Halofantrine in preclinical studies therefore appears to be an active antimalarial, with a satisfactory toxicological profile.
Url:
DOI: 10.1016/S0169-4758(89)80003-1
Affiliations:
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Schuster</name></author><author><name sortKey="Canfield, Craig J" sort="Canfield, Craig J" uniqKey="Canfield C" first="Craig J." last="Canfield">Craig J. Canfield</name></author></analytic><monogr></monogr><series><title level="j">Parasitology Today</title><title level="j" type="abbrev">PARTOD</title><idno type="ISSN">0169-4758</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1989">1989</date><biblScope unit="volume">5</biblScope><biblScope unit="supplement">S1</biblScope><biblScope unit="page" from="3">3</biblScope><biblScope unit="page" to="13">13</biblScope></imprint><idno type="ISSN">0169-4758</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0169-4758</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Adverse effect</term><term>Anaesthetized mice</term><term>Antimalarial</term><term>Antimalarial activity</term><term>Biochemical changes</term><term>Blood cells</term><term>Blood pressure</term><term>Body weight</term><term>Bone marrow</term><term>Breast milk</term><term>Clinical signs</term><term>Clinical studies</term><term>Control dams</term><term>Desbutyl</term><term>Desbutyl halofantrine</term><term>Development command contract</term><term>Dos</term><term>Dose levels</term><term>Dosing</term><term>Drug administration</term><term>Faecal extracts</term><term>Falciparum</term><term>Falciparum malaria</term><term>Female rats</term><term>Food consumption</term><term>French laboratories</term><term>Gestation</term><term>Growth rate</term><term>Halofantrine</term><term>Halofantrine hydrochloride</term><term>Heart rate</term><term>Higher doses</term><term>Hiremath</term><term>Immune function</term><term>Interim report</term><term>Laboratory evidence</term><term>Lactation</term><term>Maintenance dose</term><term>Major component</term><term>Malaria</term><term>Male mice</term><term>Male rats</term><term>Mefloquine</term><term>Metabolic activation</term><term>Mglkg</term><term>Minor component</term><term>Morphological evidence</term><term>Oral administration</term><term>Oral doses</term><term>Peak concentrations</term><term>Peak plasma concentrations</term><term>Plasmodium</term><term>Plasmodium falciparum</term><term>Preclinical</term><term>Preclinical trials</term><term>Putative metabolite</term><term>Radioactive dose</term><term>Recovery period</term><term>Reproductive performance</term><term>Reproductive studies</term><term>Research report</term><term>Same system</term><term>Seminal vesicles</term><term>Serum cholesterol</term><term>Similar studies</term><term>Skeletal anomalies</term><term>Skeletal muscle</term><term>Smith kline</term><term>Study report</term><term>Subsequent study</term><term>Synthesis report</term><term>Target organs</term><term>Teratogenic effects</term><term>Toxic signs</term><term>Toxicity</term><term>Twoweek recovery period</term><term>Unchanged drug</term><term>Unchanged halofantrine</term><term>Weight loss</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Summary: Habfantrine is one of a series of phenanthrene methanols investigated by WRAIR for us antimalarial activity. It has been shown to be highly active in vitro and to cure malaria in animal models. Its putative metabolite desbutyl halofantrine was shown to be equipotent against chloroquine-resistant and -sensitive P. falciparum strains. At present there is little evidence of cross-resistance between it and other antimalarials in human malaria species.Halofantrine is absorbed to a varying degree by animal species and is widely distributed in tissues. Elimination half-lives vary considerably among species with most of the drug apparently eliminated in the faeces. Significant changes in physiological systems were not observed.Toxicological studies, both acute and sub-acute (28 days), showed effects on a number of target organs at higher doses. No-effect doses were determined to be several times greater than expected human doses considering the systemic exposure to halofantrine. Reproductive studies showed embryotoxic but not teratogenic potential at high doses, and halofantrine was apparently excreted in breast milk. Mutagenicity studies were negative.Halofantrine in preclinical studies therefore appears to be an active antimalarial, with a satisfactory toxicological profile.</div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Canfield, Craig J" sort="Canfield, Craig J" uniqKey="Canfield C" first="Craig J." last="Canfield">Craig J. Canfield</name><name sortKey="Schuster, Brian G" sort="Schuster, Brian G" uniqKey="Schuster B" first="Brian G." last="Schuster">Brian G. Schuster</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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