I received a response from the MHLW, but......
The abortion drug Mefeego Pack, approved in Japan, has been designated a "deleterious drug" by the Japanese Ministry of Health, Labor, and Welfare. According to them, Mifepristone and Misoprostol are both "deleterious" drugs. When I asked for scientific evidence to support this, I received a response.
However, there is a part of their response that I did not understand, so I will translate it into English below.
A part of their answer I couldn't comprehend:
(i) Mifepristone
(1) The results of embryo-fetal development studies indicate that the non-toxic dose of mifepristone is 0.5 mg/kg/day for mice, 0.5 mg/kg/day for rats, and 0.25 mg/kg/day for rabbits, and that these human equivalent doses are lower than the clinical dose (4 mg/kg/day when the human body weight is 50 kg) These human equivalent doses are lower than the clinical dose (4 mg/kg/day for a 50 kg human body weight).
(See the Mefeego Pack Drug Interview Form "IX. Toxicity Studies (5) Reproductive and Developmental Toxicity Studies," p. 85)
On the interview form referred, I bolded the numbers where they matched.
(1) Female rat fertility and early embryogenesis to implantation study
Mifepristone was administered to female SD rats at a dose of 0.5 mg/animal/day (approximately 2.5 mg/kg/day) for 24 days starting 8 days before mating, and pregnancy status was evaluated the day after the last dose84) . Compared to the control group, there was no effect on the number of mated animals or pregnancy rate, but the number of implantations per pregnant rat was significantly reduced.
Tamura et al. conducted a female fertility study in which female SD rats were treated with mifepristone at doses of 0, 0.8, 4, or 20 mg/kg/day from 2 weeks prior to mating until 7 days of gestation85). The 20 mg/kg/day group showed persistent keratinization of the vaginal mucosa and arrested sexual cycle. 20 mg/kg/day for the entire period The 20 mg/kg/day group mated 10/10, all were infertile; the 20 mg/kg/day pre-mating only group mated 10/10, with 6/10 pregnant animals and increased preimplantation embryo loss rate.
The number of pregnant animals in the 20 mg/kg/day post-mating group was 0/10. 4 mg/kg/day pre-mating group showed no effect on the number of mated animals, pregnant animals, or absorbed embryos, while the post-implantation embryo loss rate increased during the entire period and in the post-mating group. Since the cessation of the sexual cycle, the decrease in the number of pregnant animals and the number of implants, and the increase in the number of absorbed embryos were due to the pharmacological effects of mifepristone, 20 mg/kg/day was considered a non-toxic dose.
(2) Embryo-fetal development studies in mice, rats, and rabbits
A study on embryo-fetal development of pregnant CD1 mice, SD rats, and HY rabbits was conducted using repeated oral administration of mifepristone during organogenesis.86),87),88) In all three species, an increase in the number of absorbed embryos (≥ 0.5 mg/kg/day in mice, ≥ 1 mg/kg/day in rats, ≥ 2 mg/kg/day in rabbits) was observed. 2 mg/kg/day or more in rabbits) were observed in all three animal species. However, no teratogenicity was observed in mice or rats. Some morphological abnormalities were observed in fetal rabbits, but the frequency of occurrence of these fetal abnormalities varied, and they were also seen in the control group, so the relationship to dosing was not clear. The non-toxic dose for the mother was considered to be 0.5 mg/kg/day for mice, 0.5 mg/kg/day for rats, 0.25 mg/kg/day for rabbits, and for embryos and fetuses, 2 mg/kg/day for mice and rats and 1 mg/kg/day for rabbits.
The first thing I couldn't understand was that at the end of (1), it says the non-toxic dose is 20 mg/kg/day, so isn't 4 mg/kg/day (i.e., the value for a 50 kg person given 200 mg of Mifepristone). This is smaller than the non-toxic dose, so Mifepristone should be non-toxic at least for this?
Also, (2) is a "repeated dose" experiment, but in humans, Mifepristone is only given once. There is no way it can be administered repeatedly. Wouldn't it be better to compare the results with those in which all animals were given only one dose in accordance with the human dosage?
Furthermore, (2) is an experiment looking at the effects on the embryo/fetus, and suddenly there is talk of a "non-toxic dose to the mother animal".
It is strange. I'll inquire again next week.
