Metabolism of [(1)(4)C]prometryn in rats.

[(1)(4)C]Prometryn, 2, 4-bis(isopropylamino)-6-(methylthio)-s-triazine, was orally administered to male and female rats at approximately 0.5 and 500 mg/kg; daily urine and feces were collected. After 3 or 7 days rats were sacrificed, and blood and selected tissues were isolated. The urine and feces extracts were characterized for metabolite similarity as well as for metabolite identification. Over 30 metabolites were observed, and of these, 28 were identified mostly by mass spectrometry and/or cochromatography with available reference standards. The metabolism of prometryn was shown to occur by N-demethylation, S-oxidation, S-S dimerization, OH substitution for NH(2) and SCH(3), and conjugation with glutathione or glucuronic acid. Rat liver microsomal incubations of prometryn were conducted and compared to the in vivo metabolism. Both in vivo and in vitro phase I metabolisms of prometryn were similar, with S-oxidation and N-dealkylation predominating. The involvement of cytochrome P-450 and flavin-containing monooxidase in the in vitro metabolism of prometryn was investigated.

Storage requirements for erythrocytes used to culture Plasmodium falciparum.

Erythrocytes stored for up to 84 days in citrate-phosphate-dextrose (CPD), CPD-adenine, saline-glucose, saline-glucose-adenine, or as packed cells were tested after varying lengths of time for suitability to support cultures of Plasmodium falciparum using the Petri dish-candle jar technique. All storage protocols were adequate for 21 to 28 days with those media containing adenine being generally better and packed cells poorer than CPD. Erythrocyte ATP contents generally correlated well with the suitability of stored erythrocytes for supporting falciparum parasite cultures. However, rejuvenation procedures, which markedly elevated ATP concentrations in erythrocytes, resulted in erythrocytes less suitable for parasite development. Erythrocytes stored between 4 to 12 days were usually somewhat less suitable than freshly collected, or after 12-plus days of storage. The presence of leucocytes undergoing disintegration during the first week of storage had no measurable effect on the suitability of the erythrocytes because both leucocyte-rich and leucocyte-poor blood portions supported parasite development equally. Likewise, leucocytes present with parasites in the cultures, had no measurable effect on parasite development.

Clinical drug-resistant falciparum malaria acquired from cultured parasites.

This is the first reported infection with Plasmodium falciparum acquired from continuous cultures of these parasites. The strain involved, FCR3, was originally isolated from The Gambia, West Africa, and was initially sensitive to chloroquine in vitro. After nearly 4 years of continuous culture without chloroquine pressure, it became resistant to chloroquine in vitro and in vivo, as demonstrated by the failure of both prophylactic and therapeutic regimens to control an accidental inoculation of parasite-infected erythrocytes.