cgp-56697 and Disease-Models--Animal

Citrus plants particularly lemon (Citrus limon L.) concoctions are ethno-medically used for treatment of infectious diseases including malaria. Therefore, we set an experiment to investigate the effects of lemon decoction in mice infected with Plasmodium berghei ANKA parasites.. Within 72 hours after initiation of treatment, the mean percentage parasitemia ± standard deviation of the CILI extract group (24.2% ± 9.83%) was lower compared to placebo group (40.0% ± 14.78%), p = 0.037. CILI extract group was found to have an increased survival rate (11 days ± 1.6 days) as compared to placebo group (8.6 days ± 3.4 days), p = 0.226. Mice in the combination group (A/LU + CILI extract) had the highest mean counts in terms of hemato-immunological parameters, whereas those in the CILI extract alone had the lowest hematocrit levels. The study also found that mice that received a combination of CILI extract and A/LU exhibited a decreased lag time with regards to time required to clear 99% of parasites (58.8 h vs. 64.2 h, p = 0.681) as compared to the A/LU alone group.. Lemon decoction demonstrated antimalarial activity in mice infected with P. berghei ANKA through parasites suppression by 39% as compared to those received placebo. However, when used alone, lemons did not suffice as a cure but in combination with standard antimalarials, lemons promoted early parasite clearance with an improved hematological parameters.

Topics: Animals; Antimalarials; Artemether, Lumefantrine Drug Combination; Citrus; Disease Models, Animal; Drug Therapy, Combination; Female; Malaria; Male; Mice; Parasitemia; Plant Extracts; Plasmodium berghei; Tanzania

The possibility of drug-drug interactions occurring during the treatment of malaria infection in human immunodeficient virus (HIV) patients receiving antiretroviral drugs is very high and limited data are available. This study reports the effect of lopinavir/ritonavir (LR) an antiretroviral drug on the antimalarial activity of standard dose of artemether/lumefantrine (AL) or artemether (AM) in a mouse model of Plasmodium berghei. The 50% effective dose (ED50) of AM alone (0.80 ± 0.15 and 2.18 ± 0.75 mg/kg) or in combination with LR (0.88 ± 0.40 and 3.53 ± 1.09 mg/kg) on days 4 and 5 post-infection was similar. In addition, treatment with a standard dose of AL alone or in combination with LR resulted in complete suppression of parasite growth. However, co-administration of LR with AL appears to be toxic resulting in lower survival of experimental animals in comparison to those treated with standard dose of AL alone.

Topics: Animals; Anti-Retroviral Agents; Antimalarials; Artemether; Artemether, Lumefantrine Drug Combination; Artemisinins; Coinfection; Disease Models, Animal; Drug Combinations; Drug Interactions; Ethanolamines; Fluorenes; HIV Infections; Lopinavir; Malaria; Mice; Plasmodium berghei; Ritonavir

Tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination) of Plasmodium vivax. During monotherapy treatment, the compound exhibits slow parasite and fever clearance times, and toxicity in glucose-6-phosphate dehydrogenase (G6PD) deficiency is a concern. Combination with other antimalarials may mitigate these concerns.. In 2005, the radical curative efficacy of tafenoquine combinations was investigated in Plasmodium cynomolgi-infected naïve Indian-origin Rhesus monkeys. In the first cohort, groups of two monkeys were treated with a three-day regimen of tafenoquine at different doses alone and in combination with a three-day chloroquine regimen to determine the minimum curative dose (MCD). In the second cohort, the radical curative efficacy of a single-day regimen of tafenoquine-mefloquine was compared to that of two three-day regimens comprising tafenoquine at its MCD with chloroquine or artemether-lumefantrine in groups of six monkeys. In a final cohort, the efficacy of the MCD of tafenoquine against hypnozoites alone and in combination with chloroquine was investigated in groups of six monkeys after quinine pre-treatment to eliminate asexual parasites. Plasma tafenoquine, chloroquine and desethylchloroquine concentrations were determined by LC-MS in order to compare doses of the drugs to those used clinically in humans.. The total MCD of tafenoquine required in combination regimens for radical cure was ten-fold lower (1.8 mg/kg versus 18 mg/kg) than for monotherapy. This regimen (1.8 mg/kg) was equally efficacious as monotherapy or in combination with chloroquine after quinine pre-treatment to eliminate asexual stages. The same dose of (1.8 mg/kg) was radically curative in combination with artemether-lumefantrine. Tafenoquine was also radically curative when combined with mefloquine. The MCD of tafenoquine monotherapy for radical cure (18 mg/kg) appears to be biologically equivalent to a 600-1200 mg dose in humans. At its MCD in combination with blood schizonticidal drugs (1.8 mg/kg), the maximum observed plasma concentrations were substantially lower than (20-84 versus 550-1,100 ng/ml) after administration of 1, 200 mg in clinical studies.. Ten-fold lower clinical doses of tafenoquine than used in prior studies may be effective against P. vivax hypnozoites if the drug is deployed in combination with effective blood-schizonticidal drugs.

Topics: Aminoquinolines; Animals; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Chloroquine; Chromatography, Liquid; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Fluorenes; Humans; Macaca mulatta; Malaria; Male; Mass Spectrometry; Mefloquine; Plasma; Plasmodium cynomolgi; Primate Diseases; Quinine; Treatment Outcome