Publication: Plasma containing artemether-pyrimethamine has ex vivo blood schizonticidal activity against Plasmodium falciparum
Issued Date
1998-06-01
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ISSN
01251562
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2-s2.0-0032083227
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Mahidol University
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SCOPUS
Bibliographic Citation
Southeast Asian Journal of Tropical Medicine and Public Health. Vol.29, No.2 (1998), 213-224
Suggested Citation
Peerapan Tan-ariya, Ratawan Ubalee, Kesara Na-Bangchang, Juntra Karbwang Plasma containing artemether-pyrimethamine has ex vivo blood schizonticidal activity against Plasmodium falciparum. Southeast Asian Journal of Tropical Medicine and Public Health. Vol.29, No.2 (1998), 213-224. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/18520
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Title
Plasma containing artemether-pyrimethamine has ex vivo blood schizonticidal activity against Plasmodium falciparum
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Abstract
Plasma samples collected at intervals from healthy volunteers, after administration of 3 drug regimens [artemether (ART) 300 mg, pyrimethamine (PYR) 100 mg, and ART 300 mg plus PYR 100 mg] were examined for blood schizonticidal activity against K1 strain and T9.94 clone of Plasmodium falciparum ex vivo. A synergistic effect against T9.94, a pyrimethamine sensitive clone, was observed in plasma collected after ART+PYR administration, when the test was carried out in low p-aminobenzoic acid, low folic acid medium. The maximum activity (Amax), expressed as equivalent dihydroartemisinin concentration, for plasma samples collected after the combined ART+PYR regimen [6,935 (1,330-13,400) nmol/l] was significantly higher than those for the single ART or PYR regimens [935 (397-2,000) and 9.9 (5.6-15.6) nmol/l, respectively]. In addition, the area under the activity curve (AUA) for the combined regimen [12,8397 (39,274-19,7901) nmol.h/l] was significantly higher than those for the single ART or PYR regimens [(3618 (1406-5597) or 334 (82.3-733.3) nmol.h/l, respectively]. Microscopic observation revealed that ART in the combined regimen exerted its inhibitory effect against all erythrocytic stages and that this occurred before effects of PYR activity. Prolongation of inhibitory effects for the combined ART+PYR regimen was shown to be due to PYR activity by comparison to the activity from the single ART regimen. Results clearly demonstrated no PYR activity against K1, a pyrimethamine resistant strain, in plasma samples collected after the single PYR regimen and the ART+PYR regimen. Microscopic examination confirmed that growth inhibition of K1 was caused by ART activity only.