Absorption, Distribution and Excretion
Medroxyprogesterone acetate appears to be well absorbed from the gastrointestinal tract. The relative oral bioavailability of medroxyprogesterone acetate suspension and tablets has not been evaluated. Plasma medroxyprogesterone acetate concentrations achieved with a 625 mg high-concentration oral suspension (Megace ES 625 mg/5 mL) after a meal were comparable to those achieved with an 800 mg unchanged formulation (200 mg/5 mL). The effect of food on the bioavailability of medroxyprogesterone acetate oral suspension has not been evaluated. Peak concentrations and AUCs of the high-concentration suspension increased by 54.8% and 43.3%, respectively, after a meal compared to fasting; peak concentrations and AUCs of the unchanged formulation increased by 12.9% and 24.4%, respectively, after a meal compared to fasting. For more complete data on absorption, distribution, and excretion of medroxyprogesterone acetate (13 items in total), please visit the HSDB records page.

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Metabolic/Metabolic Products
Megestrol acetate appears to be completely metabolized in the liver to free steroids and glucuronide conjugates of 17α-acetoxy-2α-hydroxy-6-methylpregn-4,6-diene-3,20-dione and 17α-acetoxy-6-hydroxymethylpregn-4,6-diene-3,20-dione.
Completely metabolized in the liver to free steroids and glucuronide conjugates of 17α-acetoxy-2α-hydroxy-6-methylpregn-4,6-diene-3,20-dione, and 17α-acetoxy-6-hydroxymethylpregn-4,6-diene-3,20-dione, as well as 17α-acetoxy-2α-hydroxy-6-hydroxymethylpregn-4,6-diene-3,20-dione/human, oral/biological half-life
plasma elimination half-life is 13 to 104.9 hours (mean 34.2 hours).

Interactions
Progestins may cause amenorrhea and/or galactorrhea, interfering with the efficacy of bromocriptine; concomitant use is not recommended. /Progestins/
/Researchers/ evaluated the effects of progesterone and an orally active structure-related compound, megestrol acetate, on the regulation of multidrug resistance in several multidrug-resistant human cell lines. At a concentration of 100 μM, both steroids inhibited the binding of a vinca alkaloid photoaffinity analog to P-glycoprotein in multidrug-resistant human neuroblastoma cells SH-SY5Y/VCR (cells exhibiting over 1500-fold resistance to vincristine in a tetrazolium dye assay). However, a concentration of 100 μM significantly enhanced the binding of (3)H azidopine to P-glycoprotein. Low-dose megestrol acetate was more effective than progesterone in enhancing cellular sensitivity to vincristine and increasing cellular accumulation of (3)H vincristine. The highly resistant SH-SY5Y/VCR subline exhibited significant synergistic sensitivity to both steroids. These data suggest that medroxyprogesterone acetate may be a clinically valuable modulator of multidrug resistance.

[1]. Off-Label Megestrol in Patients with Anorexia-Cachexia Syndrome Associated with Malignancy and Its Treatments. Am J Med. 2018 Jun;131(6):623-629.e1.

Therapeutic Uses
Antitumor drug, hormone; synthetic progestin. Medroxyprogesterone acetate tablets (USP) are indicated for palliative care of advanced breast cancer or endometrial cancer (i.e., recurrent, inoperable, or metastatic disease). It should not replace currently accepted treatments such as surgery, radiotherapy, or chemotherapy. /US product label includes/ Medroxyprogesterone acetate oral suspension (USP) is indicated for the treatment of anorexia, cachexia, or unexplained significant weight loss in patients with acquired immunodeficiency syndrome (AIDS). /US product label includes/ Anorexia is a common condition among patients undergoing routine hemodialysis and is a contributing factor to malnutrition. This study aimed to evaluate the efficacy of medroxyprogesterone acetate (an appetite stimulant used in cancer patients) in treating anorexia in dialysis patients. …Sixteen patients from a /a/ hemodialysis center (three of whom had diabetes) received medroxyprogesterone acetate (160 mg once daily), and anorexia was diagnosed using the Likert scale. During the study, the dialysis protocol and dosage remained unchanged. At the third month of treatment, all patients showed significant increases in dry weight (60.8 vs 58.9 kg, P<0.01), albumin concentration (4.02 vs 3.8 g/dL, P<0.05), creatinine concentration (9.73 vs 8.26 mg/dL, P<0.01), and protein catabolism rate (1.24 vs 0.97 g/kg/day, P<0.0001). Hemoglobin concentration, erythropoietin dosage, and lipid concentrations did not change significantly. One diabetic patient required an increased insulin dose, and two other patients developed mild hyperglycemia. Medroxyprogesterone acetate did not suppress pituitary hormone secretion, but adrenocorticotropic hormone (ACTH) secretion was suppressed in 3 out of 10 patients. Patient responses varied: one patient showed no response and experienced a decrease in dry weight; five patients gained very little weight (less than 1 kg); the remaining ten patients responded well, with dry weight increases ranging from 1.5 to 5.5 kg. Medroxyprogesterone acetate can improve appetite and nutritional status in patients undergoing cyclic hemodialysis with anorexia. Medroxyprogesterone acetate may induce hyperglycemia and inhibit ACTH secretion in some patients. These side effects should be evaluated when using this therapy. For more complete data on the therapeutic uses of medroxyprogesterone acetate (8 types), please visit the HSDB record page. Drug Warnings: The glucocorticoid activity of medroxyprogesterone acetate tablets has not been adequately evaluated. Clinical reports have shown that long-term use of medroxyprogesterone acetate is associated with new-onset diabetes, exacerbation of pre-existing diabetes, and significant Cushing's syndrome. Furthermore, clinical cases of adrenal insufficiency have been observed in patients receiving or discontinuing long-term medroxyprogesterone acetate therapy, regardless of whether they are under stress or not. Furthermore, adrenocorticotropic hormone (ACTH) stimulation tests have shown that asymptomatic pituitary-adrenal suppression frequently occurs in patients receiving long-term megestrol acetate treatment. Therefore, adrenal insufficiency should be considered in any patient currently receiving or discontinuing long-term megestrol acetate treatment if symptoms and/or signs suggestive of adrenal insufficiency (e.g., hypotension, nausea, vomiting, dizziness, or fatigue) occur under stress or non-stress conditions. Laboratory testing for adrenal insufficiency is strongly recommended for these patients, and replacement therapy or stress-based doses of rapid-acting glucocorticoids should be considered. Failure to recognize hypothalamic-pituitary-adrenal axis suppression can lead to death. Finally, empirical stress-based doses of rapid-acting glucocorticoids should be considered in patients currently receiving or discontinuing long-term megestrol acetate treatment in cases of stress or serious complications (e.g., surgery, infection). Close monitoring is necessary for any patient undergoing treatment for recurrent or metastatic cancer. Caution should be exercised in patients with a history of thromboembolic disease. Medroxyprogesterone acetate is contraindicated in patients with known hypersensitivity to or any of its components. It is also contraindicated in patients with known or suspected pregnancy. Medroxyprogesterone acetate has been reported to cause exacerbation of pre-existing diabetes and increase insulin requirements. For more complete data on medroxyprogesterone acetate (26 in total), please visit the HSDB records page.

C22H30O3

342.479

342.219

3562-63-8

Megestrol acetate;595-33-5;Megestrol-d5

19090

White to off-white solid powder

1.2±0.1 g/cm3

500.4±50.0 °C at 760 mmHg

270.5±26.6 °C

0.0±2.9 mmHg at 25°C

1.569

3.06

1

3

1

25

717

6

CC1=C[C@@H]2[C@H](CC[C@]3([C@H]2CC[C@@]3(C(=O)C)O)C)[C@@]4(C1=CC(=O)CC4)C

VXIMPSPISRVBPZ-NWUMPJBXSA-N

InChI=1S/C22H30O3/c1-13-11-16-17(20(3)8-5-15(24)12-19(13)20)6-9-21(4)18(16)7-10-22(21,25)14(2)23/h11-12,16-18,25H,5-10H2,1-4H3/t16-,17+,18+,20-,21+,22+/m1/s1

(8R,9S,10R,13S,14S,17R)-17-acetyl-17-hydroxy-6,10,13-trimethyl-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthren-3-one

BDH1298; BDH 1298

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)

DMSO : ~70 mg/mL (~204.40 mM)

Solubility in Formulation 1: 2.33 mg/mL (6.80 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 23.3 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 2: ≥ 2.33 mg/mL (6.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 23.3 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 3: ≥ 2.33 mg/mL (6.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 23.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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