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International Journal of Clinical... Nov 2023At our institution, patients with hematological disease who require pneumonia (PJP) prophylaxis were administered atovaquone at a low dose (750 mg/day). However, there...
OBJECTIVE
At our institution, patients with hematological disease who require pneumonia (PJP) prophylaxis were administered atovaquone at a low dose (750 mg/day). However, there have been few reports on the efficacy of low-dose atovaquone administration, and the purpose of this study is, therefore, to investigate its effectiveness.
MATERIALS AND METHODS
We investigated the expression of PJP in patients with hematological disease who received atovaquone administration. Atovaquone was administered at a low dose of 750 mg once daily, and the follow-up time was the period of PJP prophylaxis that included atovaquone administration.
RESULTS
85 patients were included in the study. The median age of the study population was 72 years (range: 33 - 97). The duration of atovaquone treatment and follow-up time were 150 days (22 - 1,018) and 258 days (22 - 1,457), respectively. In hematologic diseases, multiple myeloma was high in 31 patients and malignant lymphoma in 28 patients. No patients exhibited PJP during the observation period.
CONCLUSION
In hematological disease patients with relatively low risk of PJP, low-dose atovaquone may prevent the onset of PJP.
Topics: Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Pneumonia, Pneumocystis; Atovaquone; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination; Hematologic Diseases; Retrospective Studies
PubMed: 37622674
DOI: 10.5414/CP204368 -
Archives of Internal Medicine Feb 2011
Topics: Abnormalities, Drug-Induced; Antimalarials; Atovaquone; Cohort Studies; Cross-Sectional Studies; Denmark; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Gestational Age; Humans; Infant, Newborn; Malaria; Pregnancy; Pregnancy Complications, Parasitic; Product Surveillance, Postmarketing; Proguanil; Registries
PubMed: 21325117
DOI: 10.1001/archinternmed.2010.521 -
Journal of Travel Medicine May 1999
Topics: Atovaquone; Chemoprevention; Dose-Response Relationship, Drug; Drug Combinations; Humans; Malaria, Falciparum; Plasmodium falciparum; Proguanil; Travel
PubMed: 23573544
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Jan 2015Atovaquone is a component of Malarone, a widely prescribed antimalarial combination, that targets malaria respiration. Here we show that parasites with high-level...
Atovaquone is a component of Malarone, a widely prescribed antimalarial combination, that targets malaria respiration. Here we show that parasites with high-level resistance to an inhibitor of dihydroorotate dehydrogenase demonstrate unexpected atovaquone tolerance. Fortunately, the tolerance is diminished with proguanil, the second partner in Malarone. It is important to understand such "genetic cross talk" between respiration and pyrimidine biosynthesis since many antimalarial drug development programs target these two seemingly independent pathways.
Topics: Antimalarials; Atovaquone; Dihydroorotate Dehydrogenase; Drug Combinations; Drug Resistance; Oxidoreductases Acting on CH-CH Group Donors; Parasitic Sensitivity Tests; Plasmodium falciparum; Proguanil
PubMed: 25331708
DOI: 10.1128/AAC.02347-14 -
Bioorganic & Medicinal Chemistry Letters Sep 20092-Piperazinyl naphthoquinones (2) and 2-piperidinyl naphthoquinones (3) were designed and synthesized as new cytotoxic and apoptosis inducing agents by utilizing the...
2-Piperazinyl naphthoquinones (2) and 2-piperidinyl naphthoquinones (3) were designed and synthesized as new cytotoxic and apoptosis inducing agents by utilizing the anti-parasite drug atovaquone as lead compound. Several compounds displayed significantly improved cytotoxic activities against a panel of cancer cell lines than that of atovaquone. These compounds also induced apoptosis through activating pro-apoptotic caspases 9 and 3.
Topics: Anti-Infective Agents; Antineoplastic Agents; Apoptosis; Atovaquone; Caspase 3; Caspase 9; Cell Line, Tumor; Crystallography, X-Ray; Drug Design; Drug Screening Assays, Antitumor; Humans; Male; Molecular Conformation; Naphthoquinones; Prostatic Neoplasms
PubMed: 19632833
DOI: 10.1016/j.bmcl.2009.07.044 -
Der Internist Feb 2014Malaria is the most important infectious disease imported by travelers and migrants from tropical and subtropical areas. It is imported quite frequently. It is a...
Malaria is the most important infectious disease imported by travelers and migrants from tropical and subtropical areas. It is imported quite frequently. It is a life-threatening disease. Symptoms are nonspecific and cannot easily be distinguished from a wide range of other febrile conditions. Therefore, travel history must be taken in all patients with fever of unknown origin and malaria diagnostics must be performed immediately on suspicion of malaria. Uncomplicated falciparum malaria should be treated in the hospital with either atovaquone-proguanil or with an artemisinin-based combination preparation. If there is evidence of severe malaria, the patient must be moved to an intensive care unit. The antiparasitic agent of choice is then artesunate.
Topics: Antimalarials; Artemisinins; Artesunate; Atovaquone; Drug Therapy, Combination; Humans; Malaria; Prevalence; Proguanil
PubMed: 24399475
DOI: 10.1007/s00108-013-3390-9 -
The Journal of Antimicrobial... Sep 2017Atovaquone is one of the alternatives to trimethoprim/sulfamethoxazole for prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients. In...
OBJECTIVES
Atovaquone is one of the alternatives to trimethoprim/sulfamethoxazole for prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients. In volunteers, there was wide inter-individual variability in atovaquone bioavailability. The aim of this study was to assess the plasma concentrations of atovaquone in immunocompromised patients under PCP prophylaxis.
METHODS
Adult haematology or HIV-positive patients receiving atovaquone (750 mg oral suspension twice a day) for PCP prophylaxis were included. Plasma concentrations were assessed using UV-HPLC, around 12 h after the evening dose (Cmin) and 1-5 h after the morning dose (Cmax).
RESULTS
A total of 82 measurements were performed in 33 patients. This included 19 HSCT recipients, 7 haematology non-transplant patients and 7 HIV-positive patients. The median Cmin (IQR) was 11.3 μg/mL (6.2-27.8) and the median Cmax was 13.4 μg/mL (6.0-28.3). The Cmin and Cmax of atovaquone were not different between HIV-negative and HIV-positive patients, or between HSCT and non-HSCT patients. Atovaquone concentrations were not influenced by the co-administration of valaciclovir (n = 20) or ciclosporin (n = 11), by gut graft-versus-host disease (n = 7) or by the intake of atovaquone with food. Nineteen of the 33 (58%) patients had Cmin <15 μg/mL, a threshold associated with a low rate of clinical response in PCP treatment.
CONCLUSIONS
Atovaquone is poorly absorbed in more than half of immunocompromised patients and its bioavailability varies between individuals. These unpredictable variations raise the question of therapeutic drug monitoring, in order to identify patients with low concentrations and those who could benefit from regimen adaptation or from alternatives.
Topics: Aged; Antifungal Agents; Atovaquone; Biological Availability; Female; HIV Infections; Humans; Immunocompromised Host; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 28651341
DOI: 10.1093/jac/dkx198 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Dec 2022To investigate the effect of atovaquone on the cell cycle and apoptosis of non-Hodgkin's lymphoma Raji cells, and clarify the related mechanisms.
OBJECTIVE
To investigate the effect of atovaquone on the cell cycle and apoptosis of non-Hodgkin's lymphoma Raji cells, and clarify the related mechanisms.
METHODS
MTT assay and trypan blue dye exclusion method were used to evaluate the effect of atovaquone on the proliferation of Raji cells. After the cells were stained by PI staining, the cell cycle distribution was detected by flow cytometry. Cell apoptosis was analyzed by Annexin V/PI double binding assay. The intracellular alterations of reactive oxygen species were detected by 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The protein expression of cell cycle and apoptosis related molecules were detected by Western blot.
RESULTS
Various concentrations of atovaquone (5-40 μmol/L) inhibited the growth of Raji cells in a concentration-dependent manner (=0.951). The proliferation of Raji cells was significantly inhibited after treated by atovaquone (20 and 30 μmol/L) for 24, 48 and 72 h, which showed statistically different with that in the control group (<0.01, <0.001, <0.001). G phase arrest (<0.01, <0.001) and apoptosis (<0.01) of Raji cells was induced by atovaquone (20 and 30 μmol/L) significantly for 24 h and 48 h, respectively. The expression of p-JAK2 and p-STAT3(Y705) protein were down-regulated significantly induced by atovaquone (<0.001, <0.05). Furthermore, atovaquone treatment could induce the decreasing of antiapoptotic protein Mcl-1, Bcl-2, and Bcl-xl expression level (<0.05) and increasing of cleaved caspase-3 protein expression level. In addition, atovaquone could also induce the down-regulation of c-Myc (<0.001, <0.01) and cell cycle related molecules Cyclin D1, CDK4, and CDK6 (<0.01, <0.05) protein expression.
CONCLUSION
Atovaquone effectively inhibits cell proliferation and induces cell cycle arrest and apoptosis by suppression of STAT3 signaling pathway in Raji cells. It can be a potential therapeutic agent against non-Hodgkin's lymphoma.
Topics: Humans; Atovaquone; Cell Cycle Checkpoints; Apoptosis; Lymphoma, Non-Hodgkin
PubMed: 36476898
DOI: 10.19746/j.cnki.issn.1009-2137.2022.06.018 -
Rheumatology International Aug 2022We compared the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) with atovaquone for pneumocystis pneumonia (PCP) in patients with connective tissue...
Comparative effectiveness of trimethoprim-sulfamethoxazole versus atovaquone for the prophylaxis of pneumocystis pneumonia in patients with connective tissue diseases receiving prolonged high-dose glucocorticoids.
We compared the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) with atovaquone for pneumocystis pneumonia (PCP) in patients with connective tissue diseases (CTDs) receiving high-dose glucocorticoids. Patients with CTDs aged ≥ 18 years who were treated with a prolonged course (≥ 4 weeks) of glucocorticoids (≥ 20 mg/day prednisone) in a Japanese tertiary center between 2013 and 2017 were included. The patients were categorized into two groups: TMP-SMX and atovaquone group. Adjusted cumulative incidence of PCP was compared between the two groups after propensity score weighting for differences in confounding factors. A total of 480 patients with a prolonged high-dose glucocorticoid treatment were identified. Out of 383 patients with TMP-SMX prophylaxis, 102 (26.8%) patients experienced adverse events leading to discontinuation within 4 weeks of initiation, while no patient in the atovaquone discontinued the therapy. Two hundred eighty-one patients received TMP-SMX, while 107 received atovaquone for PCP prophylaxis. During a total of 397.0 person-years, 7 PCP cases (2 in the TMP-SMX, 5 in the atovaquone) occurred with a mortality rate of 54.5%. After adjusting for differences in baseline characteristics, the adjusted cumulative incidence of PCP was similar between the two group (HR 0.97, 95% CI 0.19-5.09, p = 0.97). Prophylactic effects for PCP in CTDs patients receiving prolonged high-dose glucocorticoids were similar between TMP-SMX and atovaquone. Atovaquone was well-tolerated with no side effects.
Topics: Atovaquone; Connective Tissue Diseases; Glucocorticoids; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 34263352
DOI: 10.1007/s00296-021-04945-w -
Antimicrobial Agents and Chemotherapy Dec 2015Our recent report of dihydroartemisinin-piperaquine failure to treat Plasmodium falciparum infections in Cambodia adds new urgency to the search for alternative...
Our recent report of dihydroartemisinin-piperaquine failure to treat Plasmodium falciparum infections in Cambodia adds new urgency to the search for alternative treatments. Despite dihydroartemisinin-piperaquine failure, and higher piperaquine 50% inhibitory concentrations (IC50s) following reanalysis than those previously reported, P. falciparum remained sensitive to atovaquone (ATQ) in vitro. There were no point mutations in the P. falciparum cytochrome b ATQ resistance gene. Mefloquine, artemisinin, chloroquine, and quinine IC50s remained comparable to those from other recent reports. Atovaquone-proguanil may be a useful stopgap but remains susceptible to developing resistance when used as blood-stage therapy.
Topics: Antimalarials; Artemisinins; Atovaquone; Base Sequence; Cambodia; DNA, Protozoan; Drug Combinations; Drug Resistance, Multiple; Humans; Malaria, Falciparum; Parasitic Sensitivity Tests; Plasmodium falciparum; Proguanil; Quinolines; Sequence Analysis, DNA; Thailand
PubMed: 26711753
DOI: 10.1128/AAC.02302-15