Absorption, Distribution and Excretion
Atinimole has been reported to have an oral bioavailability of 45% in healthy adults. The observed time to peak concentration (Tmax) is 1–2 hours. Prolonged Tmax is known in patients with malaria infection, possibly due to reduced hepatic metabolism or drug accumulation in infected erythrocytes. Atinimole exhibits flipped absorption kinetics, with a total absorption half-life of 1.04 hours. Co-administration with food increases the AUC of atinimole by 144%. An increase in Cmax of 129% was observed, but this was not statistically significant. Food can delay the time to peak concentration by 1 hour. Atinimole is eliminated by metabolism to glucuronide conjugates. Data on artemisinin elimination are scarce, but the elimination of unmetabolized artemisinin compounds in feces and urine has been reported to be negligible.
In adult patients infected with P. falciparum, the mean apparent volume of distribution of artemisinin was 0.801 L/kg, while in pediatric patients infected with P. falciparum it was 0.705 L/kg.
In adult patients infected with P. falciparum, the mean apparent clearance of artemisinin was 1.340 L/h/kg, while in pediatric patients infected with P. falciparum it was 1.450 L/h/kg.
Metabolism/Metabolites
The major metabolite of artemisinin is a glucuronide conjugate, α-artemisinin-β-glucuronide. It is primarily metabolized by UGT1A9, with UGT2B7 also involved in some metabolism.
Biological Half-Life
The elimination half-life of artemisinin has been reported to be approximately 1 hour.

Protein Binding
Artemisinin is reported to bind to plasma proteins at a rate of 44-93%. However, the identities of these proteins have not yet been disclosed.

[1].Synthesis of dihydroartemisinin using Ni/TiO2 catalyst prepared by sol gel method. Journal of Applied Pharmaceutical Science, 2014, 4(1), Article 40101.

Dihydroartemisinin (DHA) is a derivative of artemisinin. Atinibol is also a derivative of artemisinin and an antimalarial drug used to treat uncomplicated Plasmodium falciparum infection. It was first approved by the European Medicines Agency in October 2011 for use in combination with [DB13941], marketed as Eurotramesim. Artemisinin combination therapy is highly effective against malaria and is strongly recommended by the World Health Organization. Alpha-dihydroartemisinin is an antimalarial drug. Atinibol is the active metabolite of artemether, possessing antimalarial activity and potentially exhibiting insulin-modifying, anti-inflammatory, immunomodulatory, and antitumor activities. After administration of atinibol, heme released from parasite-infected erythrocytes hydrolyzes its active internal peroxide bridge, generating reactive oxygen species (ROS) and carbon-centered free radicals, thereby damaging and killing the parasite. Atinibol may also improve insulin sensitivity and alleviate insulin resistance. In addition, atinib induces 26S proteasome-mediated androgen receptor (AR) degradation, thereby reducing AR expression, which may inhibit the proliferation of androgen-responsive cells. It also reduces luteinizing hormone (LH) and testosterone levels and may improve polycystic ovary syndrome (PCOS). Furthermore, artemisinin may modulate the immune system and inhibit tumor cell proliferation through multiple apoptotic and non-apoptotic pathways.
See also: Artemisinin (note moved to).
Drug Indications

For the treatment of uncomplicated Plasmodium falciparum infection in adults, children, and infants aged 6 months and older weighing more than 5 kg. In combination with [DB13941].
FDA Label
Mechanism of Action

Artemisinin-class drugs, including artemisinin (the main active metabolite of many artemisinin-class drugs), are thought to act through a common mechanism of action. While the exact mechanism of action is not fully understood, there are many theories about how artemisinin produces its antimalarial effects. Artemisinin is thought to bind to heme within Plasmodium falciparum. The source of this heme varies depending on the life stage of the parasite. In the early cyclic stage, artemisinin is thought to bind to heme produced by the parasite's own heme biosynthesis pathway. In later stages, artemisinin may bind to heme released from hemoglobin digestion. Once bound to heme, artemisinin is thought to undergo an activation process involving the reduction cleavage of ferrous ions, thereby breaking internal peroxide bridges and generating reactive oxygen species (ROS). This ROS is thought to undergo subsequent intramolecular hydrogen extraction, generating reactive carbon radicals. These carbon radicals are considered the source of the drug's potent activity against Plasmodium falciparum, achieving this effect through alkylation of various protein targets. The nature and extent of the effect of this alkylation on the function of specific proteins are unclear. One key target studied is the sarcoplasmic reticulum/endoplasmic reticulum Ca2+ ATPase pump in Plasmodium falciparum. Artemisinin has been found to irreversibly bind to this protein and inhibit its activity, with a binding site similar to that of carotenoids. Its mechanism of action may be the same as other proteins, namely alkylation via a carbon radical intermediate. Artemisinin appears to preferentially accumulate in infected red blood cells, resulting in concentrations hundreds of times higher than in uninfected cells. This may explain why alkylation is barely observed in uninfected red blood cells.

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Pharmacodynamics
Artemisinin is thought to form a reactive carbon radical intermediate that kills Plasmodium falciparum by alkylating various proteins.

C15H24O5

284.35

284.162

81496-81-3

11358077

Typically exists as solid at room temperature

1.3±0.1 g/cm3

375.6±42.0 °C at 760 mmHg

164-165

181.0±27.9 °C

0.0±1.9 mmHg at 25°C

1.543

2.6

1

5

0

20

415

8

C[C@@H]1CC[C@H]2[C@H]([C@@H](O[C@H]3[C@@]24[C@H]1CC[C@](O3)(OO4)C)O)C

BJDCWCLMFKKGEE-KDTBHNEXSA-N

InChI=1S/C15H24O5/c1-8-4-5-11-9(2)12(16)17-13-15(11)10(8)6-7-14(3,18-13)19-20-15/h8-13,16H,4-7H2,1-3H3/t8-,9-,10+,11+,12-,13-,14-,15-/m1/s1

(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-ol

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)

Typically soluble in DMSO (e.g. 10 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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