Author: Balaji, Niveditha ; Major, Angela ; Lu, Kun ; Mochizuki‐Kashio, Makiko ; Dorrell, Craig ; Baradar, Kevin ; Grompe, Markus ; Zhang, Qingshuo ; Liu, Chih‐Wei ; Finegold, Milton ; Peters, Alexander M.

AbstractFanconi anemia (FA) is a disease caused by defective deoxyribonucleic acid (DNA) repair that manifests as bone marrow failure, cancer predisposition, and developmental defects. We previously reported that monotherapy with either metformin (MET) or oxymetholone (OXM) improved peripheral blood (PB) counts and the number and functionality of bone marrow hematopoietic stem progenitor cells (HSPCs) number in Fancd2−/− mice. To evaluate whether the combination treatment of these drugs has a synergistic effect to prevent bone marrow failure in FA, we treated cohorts of Fancd2−/− mice and wildtype controls with either MET alone, OXM alone, MET+OXM, or placebo diet from age 3 weeks to 18 months. The OXM treated animals showed modest improvements in blood parameters including platelet count (p = .01) and hemoglobin levels (p < .05). In addition, the percentage of quiescent hematopoietic stem cell (HSC) (LSK [Lin−Sca+c‐Kit+]) was significantly increased (p = .001) by long‐term treatment with MET alone. The combination of metformin and oxymetholone did not result in a significant synergistic effect in any hematopoietic parameter. Gene expression analysis of liver tissue from these animals showed that some of the expression changes caused by Fancd2 deletion were partially normalized by metformin treatment. Importantly, no adverse effects of the individual or combination therapies were observed, despite the long‐term administration. We conclude that androgen therapy is not a contraindication to concurrent metformin administration in clinical trials.Highlights

Long‐term coadministration of metformin in combination with oxymetholone is well tolerated by Fancd2−/− mice.

Hematopoietic stem cell quiescence in mutant mice was enhanced by treatment with metformin alone.

Metformin treatment caused a partial normalization of gene expression in the livers of mutant mice.

01 Sep 2023·Value in Health Regional Issues

Real-World Costs and Cost-Effectiveness Analysis of Rabbit-Antithymocyte Globulin Versus Oxymetholone in Acquired Aplastic Anemia in Thailand

Article

Author: Sripakdee, Warunsuda ; Saelue, Pirun ; Doungngern, Thitima ; Penthinapong, Thitichaya ; Tanvejsilp, Pimwara

OBJECTIVESThis study aimed to compare rabbit-antithymocyte globulin and cyclosporine (rATG/CsA) with oxymetholone in terms of direct medical expenditures and economic evaluation in severe acquired aplastic anemia (SAA) and very severe acquired aplastic anemia (vSAA) patients.METHODSPatients with SAA/vSAA who initiated treatment with rATG/CsA or oxymetholone between 2004 and 2018 were included. Trial-based cost-effectiveness evaluation in healthcare provider perspective was performed. Direct medical costs were retrieved from hospital database, inflated, and converted to 2020 US dollar (30.01 Baht per US dollar). One-way sensitivity analysis and probabilistic sensitivity analysis by nonparametric bootstrap was performed.RESULTSAfter 2-year follow-up, the total mean (SD) direct medical expenditures per patient for oxymetholone and rATG/CsA group were $8 514.48 ($12 595.67) and $41 070.88 ($22 084.04), respectively. Nevertheless, oxymetholone had significant lower survival rate than rATG/CsA (P=.001) but higher in second-year blood transfusion need (71.4% vs 18.2%) and hospitalization (14.3% vs 0%). The incremental cost-effectiveness ratio was $45 854.08 per life-year gained when rATG/CsA was used instead of oxymetholone (95% CI $24 244.03-$143 496.67 per life-year gained). The probabilistic sensitivity analysis indicated that rATG/CsA had no chance of being cost-effective for SAA/vSAA when willingness to pay threshold of one to 3 times of national gross domestic product per capita was applied.CONCLUSIONSOxymetholone remains a viable alternative in resource-limited country. Despite its high cost, the rATG/CsA is a preferred treatment option because of the significant advantages on reducing mortality, treatment complications, and hospitalization.

01 Jun 2023·Molecular and Cellular Endocrinology

Extended steroid profiling in H295R cells provides deeper insight into chemical-induced disturbances of steroidogenesis: Exemplified by prochloraz and anabolic steroids

Article

Author: Patt, Melanie ; Rudaz, Serge ; Boccard, Julien ; Odermatt, Alex ; Jager, Marie-Christin ; Winter, Denise V. ; Wey, Tim ; Gonzalez-Ruiz, Victor

Human adrenocortical H295R cells have been validated by the OECD Test Guideline 456 to detect chemicals disrupting testosterone and 17β-estradiol (estradiol) biosynthesis. This study evaluated a novel approach to detect disturbances of steroidogenesis in H295R cells, exemplified by prochloraz and five anabolic steroids. Steroid profiles were assessed by an untargeted LC-MS-based method, providing a relative quantification of 57 steroids annotated according to their accurate masses and retention times. Such a panel of steroids included several mineralocorticoids, glucocorticoids, progestins and adrenal androgens. The coverage of a high number of metabolites in this extended steroid profiling facilitated grouping of chemicals with similar effects and detecting subtler differences between chemicals. It allowed, for example, distinguishing between the effects of turinabol and oxymetholone, supposed to act similarly in a previous characterization including only nine adrenal steroids. Furthermore, the results revealed that product/substrate ratios can provide superior information on altered enzyme activities compared to individual metabolite levels. For example, the 17α-hydroxypregnenolone/pregnenolone ratio was found to be a more sensitive marker for detecting 17α-hydroxylase inhibition by prochloraz than the corresponding individual steroids. These results illustrate that chemical grouping and calculation of product/substrate ratios can provide valuable information on mode-of-action and help prioritizing further experimental work.

100 Deals associated with Oxymetholone

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KEGG	Wiki	ATC	Drug Bank
D00490	Oxymetholone	A14AA05	DB06412

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Indication	Highest Phase	Country/Location	Organization	Date
Cachexia	Phase 1	US	Unimed Pharmaceutical, Inc.	-
Fanconi Anemia	Preclinical	US	Oregon Health & Science University	06 Dec 2014

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


IAS2004	Not Applicable	HIV Seropositivity	20	Oxymetholone 50 mg	rhkpwjncxu(bcjhdgizkm) = omwshxbmpg hkhlwxlalf (wdgvbwvspn )	Positive	01 Jan 2004

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