{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T19:54:55Z","timestamp":1785354895498,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T00:00:00Z","timestamp":1498003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006259","name":"Teva Pharmaceutical Industries","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006259","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Pridopidine is an oral drug in clinical development for treatment of patients with Huntington's disease. This study examined the interactions of pridopidine with<jats:italic>in vitro<\/jats:italic>cytochrome P450 activity and characterized the effects of pridopidine on CYP2D6 activity in healthy volunteers using metoprolol as a probe substrate. The effect of food on pridopidine exposure was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The ability of pridopidine to inhibit and\/or induce<jats:italic>in vitro<\/jats:italic>activity of drug metabolizing enzymes was examined in human liver microsomes and fresh hepatocytes. CYP2D6 inhibition potency and reversibility was assessed using dextromethorphan. For the clinical assessment, 22 healthy subjects were given metoprolol 100\u00a0mg alone and concomitantly with steady\u2010state pridopidine 45\u00a0mg twice daily. Food effect on a single 90\u00a0mg dose of pridopidine was evaluated in a crossover manner. Safety assessments and pharmacokinetic sampling occurred throughout the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pridopidine was found to be a metabolism dependent inhibitor of CYP2D6, the main enzyme catalysing its own metabolism. Flavin\u2010containing monooxygenase heat inactivation of liver microsomes did not affect pridopidine metabolism\u2010dependent inhibition of CYP2D6 and its inhibition of CYP2D6 was not reversible with addition of FeCN<jats:sub>3<\/jats:sub>. Exposure to metoprolol was markedly increased when coadministered with pridopidine; the ratio of the geometric means (90% confidence interval) for maximum observed plasma concentration, and area under the plasma concentration\u2013time curve from time 0 to the time of the last quantifiable concentration and extrapolated to infinity were 3.5 (2.9, 4.22), 6.64 (5.27, 8.38) and 6.55 (5.18, 8.28), respectively. Systemic exposure to pridopidine was unaffected by food conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>As pridopidine is a metabolism\u2010dependent inhibitor of CYP2D6, systemic levels of drugs metabolized by CYP2D6 may increase with chronic coadministration of pridopidine. Pridopidine can be administered without regard to food.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13317","type":"journal-article","created":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T21:41:15Z","timestamp":1493329275000},"page":"2214-2224","source":"Crossref","is-referenced-by-count":5,"title":["Metoprolol\u2010pridopidine drug\u2013drug interaction and food effect assessments of pridopidine, a new drug for treatment of Huntington's disease"],"prefix":"10.1111","volume":"83","author":[{"given":"Laura","family":"Rabinovich\u2010Guilatt","sequence":"first","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics Teva Pharmaceutical Industries Ltd Malvern PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilach","family":"Steiner","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Pharmacokinetics Teva Pharmaceutical Industries Ltd Netanya Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Hallak","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Pharmacokinetics Teva Pharmaceutical Industries Ltd Netanya Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Pastino","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics Teva Pharmaceutical Industries Ltd Malvern PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierandrea","family":"Muglia","sequence":"additional","affiliation":[{"name":"Neuroscience Discovery Medicine UCB Pharma Chemin du Foriest Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofer","family":"Spiegelstein","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics, Teva Pharmaceutical Industries Ltd Netanya Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13348"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13347"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000086373.32347.16"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-40"},{"key":"e_1_2_10_8_1","volume-title":"A Physician's Guide to the Management of Huntington's Disease","author":"Nance M","year":"2011"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.07.023"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.102905"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.3"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-3997-8"},{"key":"e_1_2_10_13_1","first-page":"25","article-title":"The role of sigma\u20101 receptors in the pathophysiology of neuropsychiatric diseases","volume":"3","author":"Ishikawa M","year":"2010","journal-title":"J Rec Lig Chan Res"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70233-2"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182886965"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25362"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-012-0100-2"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-012-1248-z"},{"key":"e_1_2_10_19_1","unstructured":"Guideline on the investigation of Drug interactions. 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