{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:34:40Z","timestamp":1760204080603},"reference-count":11,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,6,8]],"date-time":"2005-06-08T00:00:00Z","timestamp":1118188800000},"content-version":"vor","delay-in-days":3995,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1994,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mevalonic acid is a product of the enzyme HMG\u2010CoA reductase which is essential for cholesterol biosynthesis. Fluvastatin (Sandoz compound XU 62\u2010320) is a potent inhibitor of this enzyme and, hence, mevalonic acid production. In three separate studies, oral administration of fluvastatin at 12 and 24 mg\/kg\/day to mated rats from day 15 of gestation through weaning resulted in unanticipated maternal mortality at the time of parturition and during lactation. Microscopic evaluations performed in two studies revealed significant cardiac myopathy in the dying animals. Drug\u2010related clinical signs, significant maternal body weight loss, and an increase in stillborn pups and neonatal mortality were also noted at one or both dose levels. Supplementation of fluvastatin administration with 500 mg\/kg b.i.d. of me valonic acid completely blocked and\/or ameliorated the mortality, cardiac myopathy, and other adverse effects. These studies indicate that the adverse maternal effects observed with fluvastatin before or following parturition resulted from exaggerated pharmacologic activity at the dose levels administered, i.e., inhibition of the enzyme HMG\u2010CoA reductase, its immediate product mevalonic acid, and cholesterol biosynthesis. \u00a9 1994 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/tera.1420500104","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T16:03:35Z","timestamp":1118505815000},"page":"19-26","source":"Crossref","is-referenced-by-count":23,"title":["Prevention of fluvastatin\u2010induced toxicity, mortality, and cardiac myopathy in pregnant rats by mevalonic acid supplementation"],"prefix":"10.1002","volume":"50","author":[{"given":"Roman V.","family":"Hrab","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard A.","family":"Hartman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Raymond H.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,6,8]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(88)90002-1"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)42221-7"},{"key":"e_1_2_1_4_1","first-page":"230","volume-title":"Hypolipoproteinemic activity of XU 62\u2013320, a potent competitive inhibitor of HMG\u2010CoA reductase","author":"Engstrom R. G.","year":"1988"},{"key":"e_1_2_1_5_1","first-page":"445","volume-title":"XU 62\u2010320, an HMG\u2010CoA reductase inhibitor, more potent than compactin and lovastatin","author":"Kathawala F. G.","year":"1988"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1098-1128.1991.tb00001.x"},{"key":"e_1_2_1_7_1","first-page":"498","article-title":"Toxicity of the HMG\u2010Coenzyme A reductase inhibitor, lovastatin, to rabbits","volume":"248","author":"Kornbrust D. J.","year":"1989","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(88)90003-3"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420280316"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","unstructured":"Robison R. L. W.Suter andR. H.Cox(1994)Carcinogenicity and mutagenicity studies with fluvastatin a new entirely synthetic HMG\u2010CoA reductase inhibitor. Fund. Appl. Toxicol. (manuscript accepted for publication).","DOI":"10.1093\/toxsci\/23.1.9"},{"key":"e_1_2_1_11_1","first-page":"902","volume-title":"Subchronic target organ toxicity of XU 62\u2013320 in the rat, mouse, dog and monkey","author":"Stoll R. E.","year":"1988"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2510110606"}],"container-title":["Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Ftera.1420500104","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tera.1420500104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T03:39:59Z","timestamp":1698118799000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tera.1420500104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,7]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1994,7]]}},"alternative-id":["10.1002\/tera.1420500104"],"URL":"https:\/\/doi.org\/10.1002\/tera.1420500104","archive":["Portico"],"relation":{},"ISSN":["0040-3709","1096-9926"],"issn-type":[{"value":"0040-3709","type":"print"},{"value":"1096-9926","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,7]]}}}