{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T10:20:23Z","timestamp":1782296423860,"version":"3.54.5"},"reference-count":19,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To describe a case of exacerbated mania potentially related to an interaction between lopinavir\/ritonavir and valproic acid (VPA) and propose a mechanism of action for this interaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Summary:<\/jats:title>\n                    <jats:p>A 30-year-old man with bipolar disorder and HIV initiated treatment with lopinavir\/ritonavir, zidovudine, and lamivudine. Prior to beginning therapy with these antiretrovirals, he was receiving VPA 250 mg 3 times daily, with his most recent VPA concentration measured at 495 \u03bcmol\/L. Twenty-one days after starting antiretroviral treatment, he became increasingly manic. His VPA concentration at admission was 238 \u03bcmol\/L, a 48% decrease. The daily VPA dose was increased to 1500 mg, and olanzapine was introduced. The VPA concentration following this dose escalation was 392 \u03bcmol\/L, and the patient improved clinically.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion:<\/jats:title>\n                    <jats:p>Fifty percent of VPA is metabolized by glucuronidation, 40% undergoes mitochondrial \u03b2-oxidation, and less than 10% is eliminated by the cytochrome P450 isoenzymes. Ritonavir can induce glucuronidation of several medications including ethinyl estradiol, levothyroxine, and lamotrigine. We believe that ritonavir-mediated induction of VPA glucuronidation resulted in a decrease in VPA concentrations and efficacy. An objective causality assessment suggested that the increased mania was probably related to the decrease in VPA concentration and that a possible interaction exists between lopinavir\/ritonavir and VPA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>A potential interaction exists between VPA and all ritonavir-boosted antiretroviral regimens. Clinicians should monitor patients closely for a decreased VPA effect when these medications are given concomitantly.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1345\/aph.1g418","type":"journal-article","created":{"date-parts":[[2005,12,20]],"date-time":"2005-12-20T21:28:18Z","timestamp":1135114098000},"page":"147-150","source":"Crossref","is-referenced-by-count":32,"title":["Possible Interaction Between Lopinavir\/Ritonavir And Valproic Acid Exacerbates Bipolar Disorder"],"prefix":"10.1177","volume":"40","author":[{"given":"Nancy L","family":"Sheehan","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Montr\u00e9al; Immunodeficiency Service, Montr\u00e9al Chest Institute, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jos\u00e9e","family":"Brouillette","sequence":"additional","affiliation":[{"name":"Immunodeficiency Service, Montr\u00e9al Chest Institute, Department of Psychiatry, McGill University Health Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Soleil","family":"Delisle","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, McGill University Health Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Allan","sequence":"additional","affiliation":[{"name":"Immunodeficiency Service, Montr\u00e9al Chest Institute, McGill University Health Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2006,1,1]]},"reference":[{"key":"bibr1-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006990925122"},{"key":"bibr2-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.43.s.3.5.x"},{"key":"bibr3-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(03)00076-5"},{"key":"bibr4-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1023\/A:1016028707130"},{"key":"bibr5-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.11.4328-4331.2004"},{"key":"bibr6-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199802000-00012"},{"key":"bibr7-aph.1G418","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-199920020-00005"},{"key":"bibr8-aph.1G418","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/S0090-9556(24)15240-3","volume":"27","author":"Kumar GN","year":"1999","journal-title":"Drug Metab Dispos"},{"key":"bibr9-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1097\/00042560-199811010-00001"},{"key":"bibr10-aph.1G418","unstructured":"Package insert. Norvir (ritonavir). Saint-Laurent, Qu\u00e9bec: Abbott Laboratories, October 2003."},{"key":"bibr11-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.12.013"},{"key":"bibr12-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-081X(199907)20:5<233::AID-BDD179>3.0.CO;2-5"},{"key":"bibr13-aph.1G418","author":"Bertz R","year":"2001","journal-title":"Program and abstracts of the 2nd International Workshop on Clinical Pharmacology of HIV Therapy"},{"key":"bibr14-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1998.00749.x"},{"key":"bibr15-aph.1G418","first-page":"2235","volume":"12","author":"Tseng A","year":"1998","journal-title":"AIDS"},{"key":"bibr16-aph.1G418","author":"van der Lee MJ","year":"2005","journal-title":"Program and abstracts of the 6th International Workshop on Clinical Pharmacology of HIV Therapy"},{"key":"bibr17-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1086\/381760"},{"key":"bibr18-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1345\/aph.18240"},{"key":"bibr19-aph.1G418","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1981.154"}],"container-title":["Annals of Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1345\/aph.1G418","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1345\/aph.1G418","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:11:23Z","timestamp":1777374683000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1345\/aph.1G418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["10.1345\/aph.1G418"],"URL":"https:\/\/doi.org\/10.1345\/aph.1g418","relation":{},"ISSN":["1060-0280","1542-6270"],"issn-type":[{"value":"1060-0280","type":"print"},{"value":"1542-6270","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1]]}}}