PubMed · 12183922
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Finnish Gynecological Association's task force. 2001. [Abortion].. https://pubmed.ncbi.nlm.nih.gov/12183922/
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The efficacy of trilostane in the treatment of canine pituitary-dependent hyperadrenocorticism (PDH) was evaluated in 78 dogs with the condition which were treated for up to three years. The drug appeared to be well tolerated by almost all the dogs, and only two developed clinical signs and biochemical evidence of hypoadrenocorticism. Polyuria and polydipsia completely resolved in 70 per cent of the dogs that had these problems, and skin changes resolved in 62 per cent of the dogs that had skin abnormalities. There was a significant reduction (P<0.001 in each case) in both the mean basal and post-adrenocorticotrophic hormone (ACTH) cortisol concentrations after a mean of 12.3 days of treatment. The post-ACTH cortisol concentration decreased to less than 250 nmol/litre in 81 per cent of the dogs within one month of the start of treatment and in another 15 per cent at some later time. The median survival time of the 26 dogs which died was 549 days, and 51 of the dogs were alive at the completion of the study. One was lost to follow up after 241 days treatment.
The potentiality of mifepristone as an abortifacient and contraceptive drug along with its pharmacokinetic parameters is reviewed. Mifepristone or RU486 acts as antagonist to progestational and glucocorticoid functions. It is an orally active compound with nearly 70% absorption rate but its bioavailability is reduced to around 40% because of the first-pass effect. Peak plasma concentrations of 1.9 +/- 0.8, 3.8 +/- 0.9 and 5.3 +/- 1.3 micromol/l are reached within 1-2 h after oral administration of 50, 200 and 600 mg mifepristone in women, respectively, and are maintained at relatively high level up to 48 or 72 h depending on the ingested dose. The plasma kinetics of mifepristone followed two-compartment open model with a mean alpha-half-life of 1.4h, volume of distribution 1.47 l/kg and beta-half-life of 20-30 h in most of the subjects studied. Clearance from the body was mainly through feces (83%). Biologically active mono-demethylated, di-demethylated and hydroxylated metabolites were found in plasma soon after oral administration of mifepristone. RU486 and its mono-demethylated metabolite bind to progesterone receptors with high affinity. Mifepristone-bound receptor dimers suppress transcription activation and thus, bring about anti-progestational activity that makes mifepristone a potential abortifacient and contraceptive agent. Clinical trials for termination of early pregnancy with 50-600 mg mifepristone plus a prostaglandin analogue achieved a success rate of 82-97%. However, abdominal pain, cramping, nausea, vomiting, bleeding and delay in onset of the next menstrual cycle were the side effects. Administration of 25 mg mifepristone twice 12h apart, as a post-coital contraceptive showed 100% contraceptive efficacy. A low dose of mifepristone which does not inhibit ovulation reduced fertility significantly by affecting endometrial milieu. These findings suggest that reduced dose(s) of mifepristone, 200 mg or less, may be used as a post-coital contraceptive and in combination with vaginal misoprostol for termination of early pregnancy with high efficacy and minimal or no side effects.
BACKGROUND: Prolonged vaginal bleeding is a common complaint after medical abortion. The effect of a 1 week course of daily oral misoprostol after medical abortion with mifepristone and misoprostol on the amount of post-abortal blood loss was studied. METHODS: A total of 150 women (gestation <or=63 days) were randomized to three groups using computer-generated tables. They received 200 mg oral mifepristone, followed 48 h later by 0.8 mg oral misoprostol and vaginal placebo in group A, and 0.8 mg vaginal misoprostol and oral placebo in groups B and C. In groups A and B, the women continued with oral misoprostol 0.4 mg twice daily on days 4-10, while the women in group C took placebo. The actual blood loss was measured by the alkaline haematin method. RESULTS: No significant difference in the median amount (82.8, 94.7 and 88.5 ml for A, B and C respectively) and duration (16, 15 and 16 days respectively) of vaginal bleeding was observed. The incidence of diarrhoea was significantly higher (66, 55.1 and 12.5% respectively) in the groups with oral misoprostol after abortion. CONCLUSION: A 1 week course of oral misoprostol (0.4 mg twice daily) could not decrease the duration and amount of vaginal bleeding. Further studies with a larger sample size are needed to assess whether the complete abortion rate can be improved with this regimen.