CHENODIOL

Fetal Risk Summary

Chenodiol (chenodeoxycholic acid) is a naturally occurring bile acid used orally to dissolve gallstones. No reports on the use of this drug during human pregnancy have been located.

Chenodiol is not teratogenic in animals, but fetotoxicity has occurred in some species. Studies with pregnant rats, mice, and baboons did not observe congenital malformations after in utero exposure to the agent during organogenesis (1,2 and 3). In one study using three dosage levels, dose-related hepatotoxicity was observed in dams but not in newborn rats (4). No fetal hepatotoxicity was observed in a study of rats in which the drug composed 0.25% of the maternal diet during pregnancy (5). Hepatotoxicity was observed, however, in newborn baboons and rhesus monkeys exposed to chenodiol during gestation (3,6). Extensive hemorrhagic necrosis of the adrenal glands and interstitial hemorrhage of the kidneys were also noted in the newborn rhesus monkeys (6). Theoretically, the main hepatotoxic property of chenodiol in animals is due to its principal bacterial metabolite, lithocholic acid (7). In contrast to humans that readily metabolize lithocholic acid to poorly absorbed, nontoxic compounds, animals such as rabbits, rhesus monkeys, and baboons are unable to fully form sulfate conjugates to detoxify the metabolite, and thus are susceptible to liver damage (7).

One study concluded that dihydroxy bile acids, such as chenodiol, are transferred, at least in rats, from the mother to the fetus (5). Based on the observed hepatotoxicity of this agent, the use of chenodiol is contraindicated during pregnancy.

Breast Feeding Summary

No data are available on the excretion of chenodiol into breast milk.

References

1. Kitao T, Kamishita S, Yoshikawa H, Sakaguchi M. Teratogenicity studies of chenodeoxycholic acid in rats. Yakuri to Chiryo 1982;10:3887–3901 as cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD:Johns Hopkins University Press, 1989:127.
2. Takahashi H, Miyashita T, Tozuka K. Effects of chenodeoxycholic acid, administered in the organogenetic period, on the pre- and post-natal development of rat's and mouse's offsprings. Oyo Yakuri (Pharmacometrics) 1978;15:1047–55.
3. McSherry CK, Morrissey KP, Swarm RL, May PS, Niemann WH, Glenn F. Chenodeoxycholic acid induced liver injury in pregnant and neonatal baboons. Ann Surg 1976;184:490–9.
4. Celle G, Cavanna M, Bocchini R, Robbiano L. Chenodeoxycholic acid (CDCA) versus ursodeoxycholic acid (UDCA): a comparison of their effects in pregnant rats. Arch Int Pharmacodyn Ther 1980;246:149–58.
5. Sprinkle DJ, Hassan AS, Subbiah MTR. Effect of chenodeoxycholic acid feeding during gestation in the rat on bile acid metabolism and liver morphology. Proc Soc Exp Biol Med 1984;175:386–97.
6. Heywood R, Palmer AK, Foll CV, Lee MR. Pathological changes in fetal rhesus monkey induced by oral chenodeoxycholic acid. Lancet 1973;2:1021.
7. Allan RN, Thistle JL, Hofmann AF, Carter JA. Lithocholate metabolism during chemotherapy for gallstone dissolution. 1. Serum levels of sulphated and unsulphated lithocholates. Gut 1976;17:405–12.