Proguanil
(Synonyms: 氯胍) 目录号 : GC32085
A prodrug form of cycloguanil
Cas No.:500-92-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment: |
Sertoli cells obtained from sixteen to eighteen day-old-rats are cultured and treated with 0.3 μM to 10 μM of proguanil for 5 days after which Sertoli cell viability and nuclei integrity are determined. Also, the genetic expressions of transferrin and Glial cell line-derived neurotrophic factor are assessed[4]. |
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Animal experiment: |
Rats: Groups of ten to twelve-week-old rats are administered proguanil (2.9 mg/kg body weight) daily for 5 days and 6 weeks respectively. Thereafter, body and reproductive organ weights are taken, sperm parameters are analyzed, while the histology of the testis and epididymis are carried out. Also, serum levels of testosterone, luteinizing hormone and follicle stimulating hormone are determined[4]. |
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References: [1]. Pudney M, et al. Atovaquone and proguanil hydrochloride: a review of nonclinical studies. J Travel Med. 1999 May;6 Suppl 1:S8-12. |
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Proguanil is a prodrug form of the antimalarial agent cycloguanil .1 Proguanil is metabolized by the cytochrome P450 (CYP) isoforms CYP2C19 and CYP3A to form cycloguanil in human liver microsomes. It is active against chloroquine- and quinine-resistant strains of P. falciparum alone or in combination with atovaquone with EC50 values ranging from 0.22 to 2.67 and 0.37 to 1.6 ?M, respectively.2 It reduces parasitemia in a mouse model of P. berghei infection with a minimum effective dose (MED) of 32 mg/kg.3 Formulations containing proguanil have been used in combination with atovaquone for the prevention and treatment of malaria.
1.Birkett, D.J., Rees, D., Anderson, T., et al.In vitro proguanil activation to cycloguanil by human liver microsomes is mediated by CYP3A isoforms as well as by S-mephenytoin hydroxylaseBr. J. Clin. Pharmacol.37(5)413-420(1994) 2.Thapar, M.M., Gupta, S., Spindler, C., et al.Pharmacodynamic interactions among atovaquone, proguanil and cycloguanil against Plasmodium falciparum in vitroTrans. R. Soc. Trop. Med. Hyg.97(3)331-337(2003) 3.Black, R.H., and Ray, A.P.Experimental studies of the potentiation of proguanil and pyrimethamine by dapsone using Plasmodium berghei in white miceAnn. Trop. Med. Parasitol.71(2)131-139(1977)
| Cas No. | 500-92-5 | SDF | |
| 别名 | 氯胍 | ||
| Canonical SMILES | N=C(NC1=CC=C(Cl)C=C1)NC(NC(C)C)=N | ||
| 分子式 | C11H16ClN5 | 分子量 | 253.73 |
| 溶解度 | DMSO : ≥ 33 mg/mL (130.06 mM) | 储存条件 | Store at -20°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.9412 mL | 19.706 mL | 39.412 mL |
| 5 mM | 0.7882 mL | 3.9412 mL | 7.8824 mL |
| 10 mM | 0.3941 mL | 1.9706 mL | 3.9412 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Atovaquone/Proguanil: a review of its use for the prophylaxis of Plasmodium falciparum malaria
Drugs 2003;63(6):597-623.PMID:12656656DOI:10.2165/00003495-200363060-00006.
Atovaquone/Proguanil is a fixed-dose combination tablet of two antimalarial agents and is highly effective for the prevention of Plasmodium falciparum malaria. In combination with Proguanil, the ability of atovaquone to inhibit parasitic mitochondrial electron transport is markedly enhanced. Both atovaquone and Proguanil are active against hepatic (pre-erythrocytic) stages of P. falciparum, thereby providing causal prophylaxis and eliminating the need to continue post-travel treatment beyond 7 days. Both agents are also active against erythrocytic stages of P. falciparum, thereby providing suppressive prophylaxis. Atovaquone/Proguanil is highly effective against drug-resistant strains of P. falciparum, and cross-resistance has not been observed between atovaquone and other antimalarial agents. In comparative, randomised clinical trials, there were no cases of P. falciparum malaria in nonimmune adults, adolescents and children (>/=11 kg) visiting malaria-endemic regions for Proguanil (250/100 mg in adults and dosage based on bodyweight in children <40 kg) once daily. The efficacy for the prevention of P. falciparum malaria was estimated at 100% for atovaquone/Proguanil and for mefloquine, and 70% for chloroquine plus Proguanil. In individuals (>/=11 kg) from endemic regions who may carry some immunity to malaria (semi-immune), the prophylactic efficacy rating for atovaquone/Proguanil based on placebo-controlled trials was 95-100%. Atovaquone/Proguanil is generally well tolerated by both adults and children. The most common treatment-related adverse events in placebo-controlled trials were headache and abdominal pain, which occurred at a rate similar to that observed with placebo. Atovaquone/Proguanil therapy was associated with significantly fewer gastrointestinal adverse events than chloroquine plus Proguanil, and significantly fewer neuropsychiatric adverse events than mefloquine in nonimmune individuals. Significantly fewer recipients of atovaquone/Proguanil discontinued treatment because of adverse events than individuals receiving chloroquine plus Proguanil or mefloquine (p < 0.05). Conclusion: Atovaquone/Proguanil is a fixed-dose combination antimalarial tablet that provides effective prophylaxis of P. falciparum malaria, including drug-resistant strains. Both atovaquone and Proguanil are effective against hepatic stages of P. falciparum, which means that treatment need only continue for 7 days after leaving a malaria-endemic region. Atovaquone/Proguanil was generally well tolerated and was associated with fewer gastrointestinal adverse events than chloroquine plus Proguanil, and fewer neuropsychiatric adverse events than mefloquine. Thus, atovaquone/Proguanil provides effective prophylaxis of P. falciparum malaria and compared with other commonly used antimalarial agents has an improved tolerability profile, and, overall, a more convenient dosage regimen, particularly in the post-travel period.
Atovaquone-proguanil for prophylaxis and treatment of malaria
Ann Pharmacother 2003 Sep;37(9):1266-75.PMID:12921511DOI:10.1345/aph.1C473.
Objective: To review the currently available information on atovaquone-proguanil for treatment and prophylaxis of malaria. Data sources: A MEDLINE search was conducted from 1966 to February 2003 using key phrases Malarone, atovaquone, Proguanil, and malaria. Further articles were identified from a manual search of the references of identified articles. Study selection and data extraction: English-language studies with animal and human data evaluating preclinical pharmacology, human studies on pharmacokinetics, and clinical trials were evaluated. Relevant data were extracted from identified articles. Data synthesis: Atovaquone-proguanil has been evaluated for treatment of acute, uncomplicated malaria caused by Plasmodium falciparum in 8 clinical trials. In these studies, treatment with atovaquone-proguanil led to a higher (87-100% vs. 72-88%) or equally effective (94-100% vs. 90-100%) cure rate than the comparator antimalarial agents. Atovaquone-proguanil has been evaluated for prophylaxis of malaria in 6 clinical trials. In the 4 placebo-controlled trials for semi-immune residents or nonimmune migrants, the prophylaxis success rates in the atovaquone-proguanil and placebo arms ranged from 98% to 100% and 48% to 82%, respectively. The prophylaxis with success rates were similar among the 2 arms when atovaquone-proguanil was compared with other antimalarial regimens in nonimmune travelers. Atovaquone-proguanil was well tolerated in these clinical trials. Conclusions: Atovaquone-proguanil is a safe and effective alternative to current recommended regimens for prophylaxis and treatment of malaria.
Atovaquone/Proguanil for the prophylaxis and treatment of malaria
Expert Rev Anti Infect Ther 2005 Dec;3(6):849-61.PMID:16307498DOI:10.1586/14787210.3.6.849.
Increases in international travel and escalating drug resistance have resulted in a growing number of travelers at risk of contracting malaria. Drug resistance and intolerance to standard agents such as chloroquine, sulfadoxine/pyrimethamine and mefloquine has highlighted the need for new antimalarials. The recently licensed fixed combination of atovaquone and Proguanil hydrochloride (Malarone) is a promising new agent to prevent and treat Plasmodium falciparum malaria. Randomized controlled trials have shown that atovaquone/Proguanil is well tolerated and efficacious for the prevention and treatment of drug-resistant P. falciparum malaria. Atovaquone/Proguanil is active against the liver stage of P. falciparum malaria parasites and when used as a prophylactic agent it can be discontinued shortly after leaving malaria-endemic areas, offering a clear advantage for drug adherence.
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride
J Pharm Sci 2018 Jul;107(7):1761-1772.PMID:29571740DOI:10.1016/j.xphs.2018.03.009.
Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of Proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics Classification System (BCS) classification, experimental solubility and dissolution studies were also carried out. The antimalarial Proguanil hydrochloride, effective via the parent compound Proguanil and the metabolite cycloguanil, is not considered to be a narrow therapeutic index drug. Proguanil hydrochloride salt was shown to be highly soluble according to the U.S. Food and Drug Administration, World Health Organization, and European Medicines Agency guidelines, but data for permeability are inconclusive. Therefore, Proguanil hydrochloride is conservatively classified as a BCS class 3 substance. In view of this information and the assessment of risks associated with a false positive decision, a BCS-based biowaiver approval procedure can be recommended for orally administered solid immediate release products containing Proguanil hydrochloride, provided well-known excipients are used in usual amounts and provided the in vitro dissolution of the test and reference products is very rapid (85% or more are dissolved in 15 min at pH 1.2, 4.5, and 6.8) and is performed according to the current requirements for BCS-based biowaivers.
Atovaquone/Proguanil: the need for family protection
J Travel Med 2003 May;10 Suppl 1:S8-12; discussion S21.PMID:12737754DOI:10.2310/7060.2003.35057.
An increasing number of families, including children and the elderly, are seeking more adventurous travel in exotic parts of the world. Holiday destinations now include once-remote regions such as subSaharan Africa and New Guinea. This increase in visits to tropical and subtropical regions, combined with widespread chloroquine-resistant malaria, now places millions of Western travelers at risk of infection annually. At least 30,000 travelers from industrialized countries are reported to contract malaria each year and approximately 1 in 100 travelers who acquire Plasmodium falciparum malaria will die.