Absorption, Distribution and Excretion
Food promotes absorption. Artemether and benzflumetol (benflumetobacter) is a novel and well-tolerated oral antimalarial drug, effective even against multidrug-resistant Plasmodium falciparum. …Absorption of benzflumetol varies in malaria patients and elimination is slow (half-life of 3 to 6 days). Absorption is highly dependent on co-administration with fat; therefore, absorption significantly improves after malaria recovery. This study investigated the pharmacokinetics of a fixed-dose combination of artemether and benflumetodextrin (CGP 56697) in 39 patients with acute uncomplicated falciparum malaria under three dosing regimens: Regimen A: four tablets (320 mg artemether, 1920 mg benflumetodextrin) administered at 0, 8, 24, and 48 hours; Regimen B: two tablets (160 mg artemether, 960 mg benflumetodextrin) administered at 0, 8, 24, and 48 hours; and Regimen C: four tablets (240 mg artemether, 1440 mg benflumetodextrin) administered at 0, 8, and 24 hours. All patients exhibited a rapid initial response. The median time to parasite clearance was 40, 41, and 39.5 hours for regimens A, B, and C, respectively, and the median time to defervescence was 27.8, 32, and 24.5 hours, respectively. However, parasitemia recurred in peripheral blood smears in 9 patients (2 in regimens A, 4 in regimens B, and 3 in regimen C), between days 9 and 23. The pharmacokinetic variability of benflumetob is significant, with coefficients of variation for pharmacokinetic parameters ranging from 14.9% to 144%. Absorption and elimination of benflumetob are relatively slow. The median Cmax of a single dose (first-dose) in regimen B (6.29 ng/ml/mg) was significantly higher than that in regimen A (2.6 ng/ml/mg) and regimen C (3.06 ng/ml/mg). The mean T1/2z of regimen C (2.65 hours) was significantly shorter than that of regimen A (4.5 hours) and regimen B (3.89 hours). In regimens A and B, patients with a good response to treatment had significantly higher plasma concentrations of benflumetob than those who failed treatment. ...266 Thai patients received three combination therapy regimens: Regimen A had a mean adult dose of 1920 mg for 3 days (4 doses); Regimen B had a mean adult dose of 2780 mg for 3 or 5 days (6 doses); and Regimen C had a mean adult dose of 2780 mg for 3 and 5 days (6 doses). Detailed observation was conducted on 51 hospitalized adult patients, and limited data were collected from 215 community patients of various ages. The population absorption half-life of benflumetobacter was 4.5 hours. The median peak plasma concentrations of rumefenamic acid (5th and 95th percentiles) based on the model were 6.2 (0.25 and 14.8) μg/mL after Regimen A, 9.0 (1.1 and 19.8) μg/mL after Regimen B, and 8 (1.4 and 17.4) μg/mL after Regimen C. During acute malaria, patient absorption of the drug varied significantly (coefficient of variation 150%). Absorption increased significantly with symptom relief and variability decreased, primarily due to the resumption of normal eating habits; eating before and after administration increased oral bioavailability by 108% (90% confidence interval 64%–164%) (P < 0.0001). The high-dose regimens (B and C) showed significantly higher area under the concentration-time curve (AUC) by 60% and 100%, respectively, resulting in longer durations of plasma rumefenamic acid concentrations exceeding the putative minimum inhibitory concentration (MIC) of 280 μg/mL (median 252 hours for regimen B; 298 hours for regimen C; and 204 hours for regimen A [P < 0.0001]), and higher cure rates. Oral bioavailability of rumefenamic acid is highly food-dependent, resulting in lower bioavailability in acute malaria, but significantly improving with recovery. The high cure rates of the two six-dose regimens are due to increased AUC and prolonged time that Lumefantrine concentrations remain above the vivo MIC. Metabolism/Metabolites: Primarily metabolized in the liver via cytochrome P450 3A4. The main metabolite found in plasma is desbutylLumefantrine. Biological Half-Life: ~ 4.5 days. In a study of 266 Thai patients, three combination therapy regimens were administered. Regimen A had a mean adult dose of 1920 mg of Lumefantrine, divided into four doses over three days; Regimens B and C had a mean adult dose of 2780 mg of Lumefantrine, divided into six doses over three or five days. …The population absorption half-life of Lumefantrine is 4.5 hours. ...Two hundred and sixty-six Thai patients were given three combination therapy regimens. Regimen A had a mean adult dose of rumiphenetine of 1920 mg, divided into four doses over three days; Regimens B and C had a mean adult dose of rumiphenetine of 2780 mg, divided into six doses over three or five days. ...The population absorption half-life of rumiphenetine is 4.5 hours. ...

Protein Binding

Binding rate: 99.7%

Lumefantrine belongs to the fluorene class of compounds, with the chemical name 9-(p-chlorobenzyl)-9H-fluorene, in which chlorine is substituted at positions 2 and 7, and 2-(dibutylamino)-1-hydroxyethyl is substituted at position 4. It is an antimalarial drug, often used in combination with artemisinin to treat multidrug-resistant Plasmodium falciparum malaria. Lumefantrine is a tertiary amine, belonging to the monochlorobenzene, secondary alcohol, and fluorene classes. Lumefantrine is an antimalarial drug used to treat acute uncomplicated malaria. Its efficacy is enhanced when used in combination with artemisinin. This combination therapy is effective against the erythrocyte stage of Plasmodium. It can be used to treat infections caused by Plasmodium falciparum and unidentified Plasmodium species, including infections acquired in chloroquine-resistant areas. Lumefantrine is an antimalarial drug. It is a fluorene derivative used in combination with artemisinin to treat malaria (see artemisinin-Lumefantrine combination therapy). Indications The combination therapy of rumifentin and artemisinin is indicated for the treatment of acute uncomplicated malaria caused by Plasmodium falciparum, including malaria acquired in chloroquine-resistant areas. It can also be used to treat uncomplicated malaria of unidentified Plasmodium species. It is indicated for adults and children weighing more than 5 kg. Mechanism of Action The exact mechanism by which rumifentin exerts its antimalarial effect is not fully understood. However, existing data suggest that rumifentin inhibits the formation of β-heme by forming a complex with heme and inhibits the synthesis of nucleic acids and proteins.

C30H32CL3NO

528.94

527.154

82186-77-4

Lumefantrine-d9;2477594-24-2;Lumefantrine-d18;1185240-53-2

6437380

Yellow powder

1.252

642.5±55.0 °C at 760 mmHg

129-131ºC

342.3±31.5 °C

0.0±2.0 mmHg at 25°C

1.634

11.37

1

2

10

35

671

0

C(C1C=C(Cl)C=C2/C(/C3C=C(Cl)C=CC=3C=12)=C\C1C=CC(Cl)=CC=1)(O)CN(CCCC)CCCC

DYLGFOYVTXJFJP-MYYYXRDXSA-N

InChI=1S/C30H32Cl3NO/c1-3-5-13-34(14-6-4-2)19-29(35)28-18-23(33)17-27-25(15-20-7-9-21(31)10-8-20)26-16-22(32)11-12-24(26)30(27)28/h7-12,15-18,29,35H,3-6,13-14,19H2,1-2H3/b25-15-

2-(dibutylamino)-1-[(9Z)-2,7-dichloro-9-[(4-chlorophenyl)methylidene]fluoren-4-yl]ethanol

HSDB-7210 HSDB7210 HSDB 7210

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMF : 25 mg/mL (~47.26 mM)
DMSO : ~2 mg/mL (~3.78 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.73 mM) (saturation unknown) in 10% DMF 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.73 mM) (saturation unknown) in 10% DMF 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.

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Solubility in Formulation 3: ≥ 0.2 mg/mL (0.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 2.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 4: 0.2 mg/mL (0.38 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 2.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 5: 10% DMSO + 90% Corn Oil

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 (Please use freshly prepared in vivo formulations for optimal results.)