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小丸丸9

铁虫 (正式写手)

应助: 0 (幼儿园)
金币: 777.5
散金: 77
红花: 1
帖子: 829
在线: 147.5小时
虫号: 3337955
注册: 2014-07-24
性别: MM
专业: 无机药物化学

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Reproductive toxicity studies
The reproductive toxicity of docetaxel was investigated in CD rats and NZW rahhits. In a fertility
study. male rats were treated for 70 days prior to and
through mating with daily doses of up to 1.8 mg/m2
docetaxel. while females received daily doses of up
to 1.35mg m2 from 15 days prior to mating through
day 7 of gestation
At the intermediate (0 .9 mg m2
) and (1.35 or1.8 mg/m2
) high dose levels. docetaxel produced
maternal and paternal toxicit associated with a reduction
in mean body weight (males and females). testicular weight, and a reduction in fertility param
eters , such as the number of corpora lutea and implantations,
litter size and number of live fetuses
associated with increased resorptions. Therefore.
the drug was considered to be embryotoxic at daily
doses of 0.9 mg/m2 and above. However, no external
fetal malformations were observed at any dose
level. The no-effect level in this study was 0.3 mg/m2/ day.
Pregnant rats and rabbits were treated with daily
doses of up to 1.8 mg/m2 (rat) or 2.4 mg/m2 (rabbit)
during the organogenesis phase of gestation. In rats ,
1.8 mg/m2/day produced an increase in post-implantation
loss, reduced fetal weight and a delay
in fetal ossification. No treatment-related external,
skeletal or visceral malformations were observed
and post-natal development was not affected in any
group. ln rabbits, 2.4 mg/m2/ day was lethal to most
of the dams. A dose of 1.2 mg/m2 produced marked
maternal toxicity, an increased incidence in abortions
and reduced fetal weight associated with a
delay in fetal ossification. No compound-related external,
skeletal or visceral malformations were observed
in this study. No adverse embryo-fetal
effects were noted following maternal exposure to
0.18 mg/m2 (rat) or 0.36 mg/m2 (rabbit).
In conclusion, docetaxel was non-teratogenic,
but was embryo- and fetotoxic. The increased abor
tion rate in rabbits treated with daily doses of
1.2 mg/m2 and above is a common response of rabbits
to maternal toxicity83 In addition, the results of
a fertility study and the adverse effects observed in
the testes of rats and mice indicate that docetaxel,
like paclitaxel or other antimitotic drugs , has the
potential to affect fertility。

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