{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T18:42:09Z","timestamp":1793472129872,"version":"4.5.0"},"reference-count":13,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T00:00:00Z","timestamp":1156464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p><jats:bold>Summary:\u2002<\/jats:bold>  <jats:italic>Purpose:<\/jats:italic> To determine potential changes in total and unbound serum valproic acid (VPA) concentrations at steady\u2010state during a cycle of intake of combined hormonal contraceptive (HC) steroids.<\/jats:p><jats:p> <jats:italic>Methods:<\/jats:italic> Blood samples were collected from nine women stabilized on VPA monotherapy on two separate randomized occasions: (i) at the end of the 4\u2010 to 7\u2010day HC\u2010free interval, and (ii) on the last day of the HC intake period. Trough concentrations of VPA in serum and serum ultrafiltrates were determined by fluorescence polarization immunoassay.<\/jats:p><jats:p> <jats:italic>Results:<\/jats:italic> In all women, total and unbound VPA concentrations were higher during the HC\u2010free interval than during HC intake (means \u00b1 SD: 425 \u00b1 184 vs. 350 \u00b1 145 \u03bcmol\/L, respectively, for total VPA, p = 0.002, and 55 \u00b1 37 vs. 39 \u00b1 25 \u03bcmol\/L, respectively, for unbound VPA, p = 0.005). Compared with the HC\u2010free interval, HC intake was associated with a mean 21.5% increase in VPA total apparent oral clearance (from 8.0 \u00b1 5.2 to 9.7 \u00b1 6.4 ml\/h\/kg, p = 0.01) and a 45.2 % increase in VPA unbound apparent oral clearance (from 79 \u00b1 81 to 115 \u00b1 121 ml\/h\/kg, p = 0.029).<\/jats:p><jats:p> <jats:italic>Conclusions:<\/jats:italic> The apparent oral clearance of total and unbound VPA increases during the HC intake period compared with the HC\u2010free interval, probably due to induction of glucuronosyltransferase by ethinylestradiol. The magnitude of the change varies across individuals, being potentially clinically relevant in some cases. Serum VPA concentrations should be monitored when adding or discontinuing HC steroids, and possibly during the on\u2013off intervals of a HC cycle.<\/jats:p>","DOI":"10.1111\/j.1528-1167.2006.00629.x","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T11:34:27Z","timestamp":1156505667000},"page":"1569-1572","source":"Crossref","is-referenced-by-count":54,"title":["Increased Apparent Oral Clearance of Valproic Acid during Intake of Combined Contraceptive Steroids in Women with Epilepsy"],"prefix":"10.1111","volume":"47","author":[{"given":"Carlo Andrea","family":"Galimberti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda","family":"Mazzucchelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Arbasino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paola","family":"Canevini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Fattore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Perucca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,9,13]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(03)00483-6"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200216040-00005"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199120010-00002"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(01)00305-9"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000076485.09353.7A"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02539.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2006.00558.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2005.00605.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-198612000-00005"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.22.716"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2005.10105.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20131"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1978.tb01663.x"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1528-1167.2006.00629.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1528-1167.2006.00629.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T23:56:50Z","timestamp":1697327810000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1528-1167.2006.00629.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9]]},"references-count":13,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2006,9]]}},"alternative-id":["10.1111\/j.1528-1167.2006.00629.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1528-1167.2006.00629.x","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9]]}}}