Comparative distribution and embryotoxicity of hydroxyurea in pregnant rats and rhesus monkeys.

  title={Comparative distribution and embryotoxicity of hydroxyurea in pregnant rats and rhesus monkeys.},
  author={J. Gerald Wilson and William J. Scott and E. J. Ritter and Rochelle Fradkin},
  volume={11 2},
Hydroxyurea was given to pregnant rhesus monkeys and pregnant rats in regimens adjusted to produce similar degrees of teratogenicity, for the purpose of comparing the distribution of the drug in the females and their embryos. According, in rats 137 mg/kg/day ip on days 9-12 resulted in a drug half-life in maternal plasma of about 15 min and in embryos about 85 min, after the last injection; and in monkeys 100 mg/kg/days iv on days 23-32 resulted in drug half-life in maternal plasma estimated to… 
Comparative distribution and embryotoxicity of methotrexate in pregnant rats and rhesus monkeys.
A slow rate of fall in embryo concentrations in both species was estimated to be inversely proportioned to the rate of growth of embryos, which was in accord with the fact that the absolute amount per embryo was little changed in 24 hours.
Consideration of Pharmacokinetics and Temporal Sensitivity for Hydroxyurea in Relation to Teratogenic Potential
A compartmental pharmacokinetic-mathematical model for the time-dependent distribution of hydroxyurea in both the maternal plasma and embryonic fluids of pregnant rats and rhesus monkeys was developed and the temporal susceptibility for ongoing clinical trials of HU in the treatment of sickle cell anemia was reviewed.
A teratogenicity study on hydroxyurea and diphenylhydantoin in cats.
Hydroxyurea and diphenylhydantoin gave no clear evidence of teratogenicity at any test dose but was embryolethal at the maternally toxic dose of 2 mg/kg, suggesting that the cat is a useful species for screening drugs and chemicals for their teratogenic potential.
Hydroxyurea as a reference standard in teratological screening. Comparison of the embryotoxic and teratogenic effects following single intraperitoneal or repeated oral administrations to pregnant rats.
This experiment demonstrated the high susceptibility of the genotype of the colony of rats to the embryotoxic potential of HU, which led to a dose dependent embryolethal and teratogenic effect.
Effects of prenatal hydroxyurea-treatment on mouse offspring.
  • G. Woo, K. Katayama, K. Doi
  • Medicine, Biology
    Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie
  • 2004
In utero morphological effects of hydroxyurea on the fetal development in Sprague-Dawley rats.
Such morphological effects of HU as the exencephaly, dilatation of lateral ventricle, anophthalmia, cleft palate and micrognathia are less severe in Sprague-Dawley rat Fetuses than in Wistar rat fetuses.
Tolerability and age‐dependent toxicokinetics following perinatal hydroxyurea treatment in Sprague Dawley rats
The toxicokinetic studies suggest that the internal dose in offspring may be altered due to age, but not due to sex, and the plasma area under the curve, a measure of systemic exposure, at doses tolerated by offspring was threefold to sevenfold lower than the internal therapeutic dose in humans.
Behavioral Effects of Hydroxyurea Exposure during Organogenetic Period of the Sprague‐Dawley Rats
It is suggested that the morphological and behavioral effects of HU in SD male rats are less severe than those in Wistar male rats as was in the previous study.
Teratologic potential of 2-methoxyethanol and transplacental distribution of its metabolite, 2-methoxyacetic acid, in non-human primates.
It is indicated that 2-ME is a potent toxin to the developing primate embryo and thereby furthers the concern about exposure of pregnant women to this agent, although maternal toxicity was evident in nearly all treated pregnancies and was especially severe in the high-dosage animals.


The effects of hydroxyurea and related compounds on the rat fetus.
The similarity in the spectra of abnormalities produced by hydroxyurea, hydroxyUREthan, and acetohydroxamic acid at biologically comparable doses suggest that these compounds may have a common mechanism of action.
Breeding and pregnancy in rhesus monkeys used for teratological testing.
Clomiphene citrate did not improve conception rate in relatively infertile animals above that observed in untreated animals with similar reproductive histories, and early abortions after teratological tests were diagnosed by uterine palpation.
Hydroxyurea. I. Acute cell death in proliferating tissues in rats.
The lethal effects of the hydroxamates are restricted to cells committed to DNA synthesis, and other cells in proliferating tissues escape damage during the limited time of circulation of inhibitory concentrations; this accounts for the prompt repair of tissue defects.
An in vitro study of functions of embryonic membranes in the rat.
It is concluded that the outer membranes and the visceral yolk sac play an important role in the transfer of small metabolites to the embryo, as well as in regulating the volume of the extraembryonic fluids.
The production of congenital malformations using tissue antisera. VII. Yolk-sac antiserum.
Fluorescence-labeling techniques revealed that yolk-sac antiserum contained antibodies that reacted strongly with the nonserum-protein antigens of maternal adrenal, ovary, and kidney; fetal yolk sac; and chorioallantoic placenta.
Problems in Predicting Drug Effects across Species Lines
In cases where the drug in question has a potentially major therapeutic use in man, it is suggested that the data be evaluated on the basis of a pragmatic benefit-to-risk ratio, rather than zero-toxicity, so that drug therapy for those patients for whom adequate treatment does not exist is provided.
Incorporation of 3H-thymidine in rhesus monkey (Macaca mulatta) embryos.
A procedure has been developed whereby cell proliferation during early embryogenesis of the monkey can be studied radioautographically following in vivo exposure to relatively small amounts of