阿格列酮
黃體素受體拮抗劑
阿格列酮是一種合成類固醇，作為**黃體素受體拮抗劑**。主要用於獸醫學中犬貓的**終止妊娠**，以及內科治療**子宮蓄膿**和貓的**纖維腺瘤性乳腺增生**。 由於其基質為油醇混合物，局部注射部位反應相當常見。 **臨床要點**：作為競爭性拮抗劑，阿格列酮不會降低體內循環的黃體素濃度，而是直接在受體層次阻斷黃體素的生物學作用。
作用機制: Aglepristone competitively binds to **progesterone (P4) receptors** in the uterus and other target tissues. * In dogs, its affinity for uterine progesterone receptors is ~3x that of endogenous progesterone; in queens, it is ~9x greater. * **Pathway**: Aglepristone binding → blockade of progesterone signaling → withdrawal of pregnancy support → cervical dilation and resumption of myometrial contractility → fetal resorption or abortion (usually within 7 days). * It also binds to **glucocorticoid receptors** acting as an antagonist, which can block endogenous or exogenously administered glucocorticoids from acting at these sites.
各物種劑量
Dogs
- To terminate pregnancy (up to day 45) · 10 mg/kg (0.33 mL/kg) subcutaneous injection only. Repeat one time, 24 hours after the first injection. · SC · q24h · 2 doses · A maximum of 5 mL should be injected at any one site. Light massage of the injection site is recommended.
- To induce parturition · At day 60 (post-estimated LH surge): 15 mg/kg SC and another dose 24 hours later. Subsequently, give oxytocin 0.15 Units/kg SC at hourly intervals until last pup is delivered. · SC · q24h · 2 doses · Additional studies confirming efficacy and safety are warranted before routine clinical application.
- To induce parturition · On or after day 58 of pregnancy: 15 mg/kg subcutaneously; repeat in 9 hours. · SC · Repeat in 9 hours · 2 doses · Expulsion of first pup occurred between 32 and 56 hours after treatment. Use standard protocols to assist with birth.
- As an adjunct to treating pyometra/metritis (preserve fertility) · Treatment begun at week 2-4 of diestrus with a single SC injection of aglepristone at 10 mg/kg. Doses are repeated at days 2, 7, and 14. · SC · Days 1, 2, 7, 14 · 14 days · During first 7 days, daily injections of amoxicillin/clavulanic acid were also given.
- For closed cervix pyometra · 6 mg/kg twice daily on the first day followed by the same dose once daily on days 2, 3, and 4. Some prefer using larger doses (10mg/kg) once daily on days 1, 3, and 8, then follow up also on days 15 and 28 depending on the bitch's condition. · SC · Variable · Variable
- For metritis · 10 mg/kg subcutaneously once daily on days 1, 2 and 8. · SC · Days 1, 2, 8 · 8 days
- For open or closed pyometra · aglepristone 10 mg/kg subcutaneously once daily on days 1, 2 and 8 and cloprostenol 1 microgram/kg subcutaneously on days 3 to 7. · SC · Days 1, 2, 8 · 8 days · Bitches with closed pyometra or with elevated temperature/dehydration should also receive IV fluids and antibiotics. If unresolved, additional doses on days 14 and 28.
- For pyometra · 10 mg/kg SC on days 1, 2, 8, 15, & 29. Give misoprostol 10 micrograms/kg PO twice daily on days 3 through 12. · SC · Days 1, 2, 8, 15, 29 · 29 days · Approximately 75% of cases show significant clinical improvement without developing adverse effects associated with prostaglandins.
- Pregnancy termination · 10 mg/kg · SC · q24h · 2 doses · Maximum of 5 ml injected at any one site.
- Progesterone-induced acromegaly · 10 mg/kg · SC · q24h for 2 doses, then q7d · 5 doses total · Maximum of 5 ml injected at any one site.
- Pyometra · 10 mg/kg · SC · Days 1, 2, and 7 · 3 doses (up to 5) · Maximum of 5 ml injected at any one site. Additional doses may be given on days 14 and 21 if there is an inadequate response.
Cats
- For treating mammary fibroadenomatous hyperplasia · 20 mg/kg aglepristone subcutaneously once weekly until resolution of signs. · SC · q7d · Until resolution · Cats with HR > 200 BPM should receive atenolol at 6.25 mg (total dose) until HR < 200 BPM with regression in mammary gland size.
- For treating mammary fibroadenomatous hyperplasia · 10 mg/kg SC on two consecutive days, once weekly. · SC · Two consecutive days weekly · 3-5 weeks · Complete regression occurs on average 3-4 weeks. Relapses can occur, particularly if treated with long-acting progestins; these cats should be treated for 5 weeks.
- To terminate pregnancy (up to day 45) · 15 mg/kg SC twice 24 hours apart. · SC · q24h · 2 doses · Efficacy is 95% if administered before implantation, 85% if after implantation. Termination occurs within 3 days in 50% of queens.
- Pregnancy termination · 15 mg/kg · SC · q24h · 2 doses · Maximum of 5 ml injected at any one site.
- Fibroadenomatous hyperplasia · 20 mg/kg · SC · q7d · Until resolution · Maximum of 5 ml injected at any one site. Consider atenolol if cat is tachycardic with heart rate >200 bpm.
- Pyometra · 15 mg/kg · SC · Days 1, 2, and 7 · 3 doses (up to 5) · Maximum of 5 ml injected at any one site. Additional doses may be given on days 14 and 21 if there is an inadequate response.
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
SC
禁忌症
- Known hypersensitivity to aglepristone
- Pregnancy (unless used specifically for pregnancy termination or inducing parturition)
- Hypoadrenocorticism (Addison's disease) or genetic predisposition to it
- Peritonitis (must be ruled out before using for pyometra)
- Caution in patients with poor health, diabetes, or impaired hepatic/renal function
不良反應
- Injection site reactions (pain, edema, skin thickening, ulceration, localized lymph node enlargement)
- Anorexia (25%)
- Excitation (23%)
- Depression (21%)
- Diarrhea (13%)
- Uterine infections (3.4%)
- Vomiting (2%)
- Brown mucoid vaginal discharge (associated with pregnancy termination)
- Mammary gland congestion
藥物相互作用
- Progestins (natural or synthetic) · Could reduce the efficacy of aglepristone
- Glucocorticoids · Aglepristone could reduce the efficacy of glucocorticoid treatment due to receptor antagonism · moderate
- Ketoconazole · May interact with aglepristone (manufacturer warning, likely due to CYP450 enzyme inhibition)
- Itraconazole · May interact with aglepristone (manufacturer warning)
- Erythromycin · May interact with aglepristone (manufacturer warning)
監測
- Clinical efficacy
- For pregnancy termination: ultrasound 10 days after treatment and at least 30 days after mating
- Injection site reactions (pain, swelling, ulceration)
- Systemic adverse effects (anorexia, excitation, depression, diarrhea)
過量
When administered at 3X (30 mg/kg) recommended doses, bitches demonstrated no untoward systemic effects. Localized reactions were noted at the injection site, presumably due to the larger volumes injected.
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