{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:25:12Z","timestamp":1784733912688,"version":"3.55.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>The psychedelic alkaloid ibogaine is increasingly used as an oral treatment for substance use disorders, despite being unlicensed in most countries and having reported adverse events. Using wild-type and genetically modified mice, we investigated the impact of mouse (m)Abcb1a\/1b and Abcg2 drug efflux transporters, human and mouse OATP drug uptake transporters, and the CYP3A drug-metabolizing complex on the pharmacokinetics of ibogaine and its main metabolites. Following oral ibogaine administration (10\u00a0mg\/kg) to mice, we observed a rapid and extensive conversion of ibogaine to noribogaine (active metabolite) and noribogaine glucuronide. Mouse Abcb1a\/1b, in combination with mAbcg2, modestly restricted the systemic exposure (plasma AUC) and peak plasma concentration (C<jats:sub>max<\/jats:sub>) of ibogaine. Accordingly, we found a \u223c2-fold decrease in the relative recovery of ibogaine in the small intestine with fecal content in the absence of both transporters compared to the wild-type situation. Ibogaine presented good intrinsic brain penetration even in wild-type mice (brain-to-plasma ratio of 3.4). However, this was further increased by 1.5-fold in <jats:italic>Abcb1a\/1b;Abcg2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice, but not in <jats:italic>Abcg2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice, revealing a stronger effect of mAbcb1a\/1b in restricting ibogaine brain penetration. The studied human OATP transporters showed no major impact on ibogaine plasma and tissue disposition, but the mOatp1a\/1b proteins modestly affected the plasma exposure of ibogaine metabolites and the tissue disposition of noribogaine glucuronide. No considerable role of mouse Cyp3a knockout or transgenic human CYP3A4 overexpression was observed in the pharmacokinetics of ibogaine and its metabolites. In summary, ABCB1, in combination with ABCG2, limits the oral availability of ibogaine, possibly by mediating its hepatobiliary and\/or direct intestinal excretion. Moreover, ABCB1 restricts ibogaine brain penetration. Variation in ABCB1\/ABCG2 activity due to genetic variation and\/or pharmacologic inhibition might therefore affect ibogaine exposure in patients, but only to a limited extent. The insignificant impact of human CYP3A4 and OATP1B1\/1B3 transporters may be clinically advantageous for ibogaine and noribogaine use, as it decreases the risks of undesirable drug interactions or interindividual variation related to CYP3A4 and\/or OATP activity.<\/jats:p>","DOI":"10.3389\/fphar.2022.855000","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T09:58:11Z","timestamp":1646387891000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Drug Transporters ABCB1 (P-gp) and OATP, but not Drug-Metabolizing Enzyme CYP3A4, Affect the Pharmacokinetics of the Psychoactive Alkaloid Ibogaine and its Metabolites"],"prefix":"10.3389","volume":"13","author":[{"given":"Margarida L.","family":"F. Martins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paniz","family":"Heydari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Mart\u00ednez-Ch\u00e1vez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikkie","family":"Venekamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Lebre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos H.","family":"Beijnen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred H.","family":"Schinkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1007\/s12024-020-00342-0","article-title":"Death Due to Consumption of Ibogaine: Case Report","volume":"17","author":"A\u0107imovi\u0107","year":"2021","journal-title":"Forensic Sci. Med. Pathol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jep.2007.08.034","article-title":"The Ibogaine Medical Subculture","volume":"115","author":"Alper","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0099-9598(01)56005-8","article-title":"Chapter 1 Ibogaine: a Review","volume":"56","author":"Alper","year":"2001","journal-title":"Alkaloids Chem. Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1056\/NEJMc1917344","article-title":"Serious Ivermectin Toxicity and Human ABCB1 Nonsense Mutations","volume":"383","author":"Baudou","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B5","first-page":"531","article-title":"In Vivo neurobiological Effects of Ibogaine and its O-Desmethyl Metabolite, 12-hydroxyibogamine (Noribogaine), in Rats","volume":"297","author":"Baumann","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1080\/10837450902891295","article-title":"Drug Metabolism and Pharmacokinetics","volume":"41","author":"Benedetti","year":"2009","journal-title":"Drug Metab. Rev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1517\/14622416.3.2.229","article-title":"CYP2D6 Allele Frequency in European Caucasians, Asians, Africans and Their Descendants","volume":"3","author":"Bradford","year":"2002","journal-title":"Pharmacogenomics"},{"key":"B8","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1080\/00952990.2017.1320802","article-title":"Treatment of Opioid Use Disorder with Ibogaine: Detoxification and Drug Use Outcomes","volume":"44","author":"Brown","year":"2018","journal-title":"Am. J. Drug Alcohol. Abuse"},{"key":"B9","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1080\/02791072.2019.1598603","article-title":"Ibogaine and Subjective Experience: Transformative States and Psychopharmacotherapy in the Treatment of Opioid Use Disorder","volume":"51","author":"Brown","year":"2019","journal-title":"J. Psychoactive Drugs"},{"key":"B10","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2174\/15672050113109990001","article-title":"Ibogaine in the Treatment of Substance Dependence","volume":"6","author":"Brown","year":"2013","journal-title":"Curr. Drug Abuse Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/bs.pbr.2018.08.005","article-title":"Ibogaine as a Treatment for Substance Misuse: Potential Benefits and Practical Dangers","author":"Corkery","year":"2018","journal-title":"Prog. Brain. Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1080\/02791072.2018.1487607","article-title":"A Mixed-Method Analysis of Persisting Effects Associated with Positive Outcomes Following Ibogaine Detoxification","volume":"50","author":"Davis","year":"2018","journal-title":"J. Psychoact. Drugs"},{"key":"B13","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1556\/2054.01.2016.001","article-title":"The Antiaddictive Effects of Ibogaine: A Systematic Literature Review of Human Studies","volume":"1","author":"dos Santos","year":"2017","journal-title":"J. Psychedelic Stud."},{"key":"B15","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/j.bbapap.2009.02.014","article-title":"A Synonymous Polymorphism in a Common MDR1 (ABCB1) Haplotype Shapes Protein Function","volume":"1794","author":"Fung","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"B16","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nrd3028","article-title":"Membrane Transporters in Drug Development","volume":"9","author":"Giacomini","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"B17","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1111\/j.1749-6632.1998.tb08237.x","article-title":"Mechanisms of Antiaddictive Actions of Ibogaine","volume":"844","author":"Glick","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S0099-9598(01)56006-X","article-title":"Chapter 2 Mechanisms of Action of Ibogaine: Relevance to Putative Therapeutic Effects and Development of a Safer Iboga Alkaloid Congener","volume":"56","author":"Glick","year":"2001","journal-title":"Alkaloids Chem. Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/jcph.404","article-title":"Ascending-Dose Study of Noribogaine in Healthy Volunteers: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability","volume":"55","author":"Glue","year":"","journal-title":"J. Clin. Pharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1002\/jcph.471","article-title":"Influence of CYP2D6 Activity on the Pharmacokinetics and Pharmacodynamics of a Single 20 Mg Dose of Ibogaine in Healthy Volunteers","volume":"55","author":"Glue","year":"","journal-title":"J. Clin. Pharmacol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1002\/cpdd.254","article-title":"Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients","volume":"5","author":"Glue","year":"2016","journal-title":"Clin Pharmacol Drug Dev"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev.pharmtox.39.1.1","article-title":"Cytochrome P-450 3A4: Regulation and Role in Drug Metabolism","volume":"39","author":"Guengerich","year":"1999","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1523\/JNEUROSCI.3959-04.2005","article-title":"Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-addiction Drug Ibogaine against Alcohol Consumption","volume":"25","author":"He","year":"2005","journal-title":"J. Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1080\/15563650.2017.1287372","article-title":"Toxicokinetics of Ibogaine and Noribogaine in a Patient with Prolonged Multiple Cardiac Arrhythmias after Ingestion of Internet Purchased Ibogaine","volume":"55","author":"Henstra","year":"2017","journal-title":"Clin. Toxicol. (Phila)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.clpt.2005.05.011","article-title":"Transporters and Drug Therapy: Implications for Drug Disposition and Disease","volume":"78","author":"Ho","year":"2005","journal-title":"Clin. Pharmacol. Ther."},{"key":"B25","doi-asserted-by":"publisher","first-page":"PL119","DOI":"10.1016\/0024-3205(95)02322-4","article-title":"Tissue Distribution of Ibogaine after Intraperitoneal and Subcutaneous Administration","volume":"58","author":"Hough","year":"1996","journal-title":"Life Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.tips.2011.10.005","article-title":"Functions of OATP1A and 1B Transporters In Vivo: Insights from Mouse Models","volume":"33","author":"Iusuf","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1634\/stemcells.2005-0150","article-title":"Contribution of the ABC Transporters Bcrp1 and Mdr1a\/1b to the Side Population Phenotype in Mammary Gland and Bone Marrow of Mice","volume":"23","author":"Jonker","year":"2005","journal-title":"Stem Cells"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1093\/jnci\/92.20.1651","article-title":"Role of Breast Cancer Resistance Protein in the Bioavailability and Fetal Penetration of Topotecan","volume":"92","author":"Jonker","year":"2000","journal-title":"J. Natl. Cancer Inst."},{"key":"B29","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1111\/j.1476-5381.2009.00430.x","article-title":"Impact of OATP Transporters on Pharmacokinetics","volume":"158","author":"Kalliokoski","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.3390\/molecules20022208","article-title":"The Anti-addiction Drug Ibogaine and the Heart: A Delicate Relation","volume":"20","author":"Koenig","year":"2015","journal-title":"Molecules"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1023\/b:pham.0000045245.21637.d4","article-title":"Functional Analysis of SNPs Variants of BCRP\/ABCG2","volume":"21","author":"Kondo","year":"2004","journal-title":"Pharm. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.jchromb.2005.06.018","article-title":"Quantitation of Ibogaine and 12-Hydroxyibogamine in Human Plasma by Liquid Chromatography with Fluorimetric Detection","volume":"822","author":"Kontrimavici\u016bte","year":"2005","journal-title":"J. Chromatogr. B Analyt Technol. Biomed. Life Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jchromb.2006.05.035","article-title":"Liquid Chromatography-Electrospray Mass Spectrometry Determination of Ibogaine and Noribogaine in Human Plasma and Whole bloodApplication to a Poisoning Involving Tabernanthe Iboga Root","volume":"843","author":"Kontrimaviciute","year":"2006","journal-title":"J. Chromatogr. B"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/S0169-409X(02)00066-2","article-title":"Genetic Contribution to Variable Human CYP3A-Mediated Metabolism","volume":"54","author":"Lamba","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1016\/j.apsb.2019.10.001","article-title":"Current Trends in Drug Metabolism and Pharmacokinetics","volume":"9","author":"Li","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"B36","doi-asserted-by":"publisher","first-page":"59","DOI":"10.2165\/00003088-200342010-00003","article-title":"Role of P-Glycoprotein in Pharmacokinetics: Clinical Implications","volume":"42","author":"Lin","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"B37","doi-asserted-by":"publisher","first-page":"297","DOI":"10.3109\/15563650.2016.1138226","article-title":"How Toxic Is Ibogaine?","volume":"54","author":"Litjens","year":"2016","journal-title":"Clin. Toxicol. (Phila)"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1080\/17425255.2021.1944099","article-title":"Evaluating the Toxicity and Therapeutic Potential of Ibogaine in the Treatment of Chronic Opioid Abuse","volume":"17","author":"Luz","year":"2021","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1177\/0960327107087802","article-title":"Ibogaine, an Anti-addictive Drug: Pharmacology and Time to Go Further in Development. A Narrative Review","volume":"27","author":"Ma\u010diulaitis","year":"2008","journal-title":"Hum. Exp. Toxicol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1208\/s12248-014-9668-6","article-title":"Role of the Breast Cancer Resistance Protein (BCRP\/ABCG2) in Drug Transport-An Update","volume":"17","author":"Mao","year":"2015","journal-title":"AAPS J."},{"key":"B41","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3389\/fphar.2019.00193","article-title":"Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits","volume":"10","author":"Marton","year":"2019","journal-title":"Front. Pharmacol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"PL45","DOI":"10.1016\/0024-3205(95)00273-9","article-title":"Identification of a Primary Metabolite of Ibogaine that Targets Serotonin Transporters and Elevates Serotonin","volume":"57","author":"Mash","year":"1995","journal-title":"Life Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/j.1749-6632.2000.tb05213.x","article-title":"Ibogaine: Complex Pharmacokinetics, Concerns for Safety, and Preliminary Efficacy Measures","volume":"914","author":"Mash","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/S0099-9598(01)56012-5","article-title":"Chapter 8 Ibogaine in the Treatment of Heroin Withdrawal","author":"Mash","year":"2001","journal-title":"Alkaloids: Chem. Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"529","DOI":"10.3389\/fphar.2018.00529","article-title":"Ibogaine Detoxification Transitions Opioid and Cocaine Abusers between Dependence and Abstinence: Clinical Observations and Treatment Outcomes","volume":"9","author":"Mash","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/00952990.2017.1357184","article-title":"Breaking the Cycle of Opioid Use Disorder with Ibogaine","volume":"44","author":"Mash","year":"2018","journal-title":"Am. J. Drug Alcohol. Abuse"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1177\/002215540205001008","article-title":"Expression and Localization of P-Glycoprotein in Human Heart: Effects of Cardiomyopathy","volume":"50","author":"Meissner","year":"2002","journal-title":"J. Histochem. Cytochem."},{"key":"B48","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1369\/jhc.5A6750.2005","article-title":"The ATP-Binding Cassette Transporter ABCG2 (BCRP), a Marker for Side Population Stem Cells, Is Expressed in Human Heart","volume":"54","author":"Meissner","year":"2006","journal-title":"J. Histochem. Cytochem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1002\/cpt.1135","article-title":"CYP2D6 Genotype Phenotype Discordance Due to Drug-Drug Interaction","volume":"104","author":"Monte","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"B50","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A Simple Practice Guide for Dose Conversion between Animals and Human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"B51","doi-asserted-by":"publisher","first-page":"787","DOI":"10.2217\/14622416.8.7.787","article-title":"Role of OATP Transporters in the Disposition of Drugs","volume":"8","author":"Niemi","year":"2007","journal-title":"Pharmacogenomics"},{"key":"B52","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1080\/00952990.2017.1310218","article-title":"Ibogaine Treatment Outcomes for Opioid Dependence from a Twelve-Month Follow-Up Observational Study","volume":"44","author":"Noller","year":"2018","journal-title":"Am. J. Drug Alcohol. Abuse"},{"key":"B53","first-page":"764","article-title":"Cytochrome P4502D6 Catalyzes the O-Demethylation of the Psychoactive Alkaloid Ibogaine to 12-hydroxyibogamine","volume":"26","author":"Obach","year":"1998","journal-title":"Drug Metab. Dispos."},{"key":"B54","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1080\/10837450902890958","article-title":"Importance of Knowledge on Drug Metabolism for the Safe Use of Drugs in Humans","volume":"41","author":"Oesch","year":"2009","journal-title":"Drug Metab. Rev."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-021-05964-y","article-title":"The Adverse Events of Ibogaine in Humans: an Updated Systematic Review of the Literature (2015\u20132020)","author":"Ona","year":"2021","journal-title":"Psychopharmacology (Berl)"},{"key":"B56","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/S0091-3057(96)00383-8","article-title":"Sex Differences in Ibogaine Antagonism of Morphine-Induced Locomotor Activity and in Ibogaine Brain Levels and Metabolism","volume":"57","author":"Pearl","year":"1997","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B57","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1177\/0269881114552713","article-title":"Treating Drug Dependence with the Aid of Ibogaine: A Retrospective Study","volume":"28","author":"Schenberg","year":"2014","journal-title":"J. Psychopharmacol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.drugalcdep.2016.07.005","article-title":"Ibogaine for Treating Drug Dependence. What Is a Safe Dose?","volume":"166","author":"Schep","year":"2016","journal-title":"Drug Alcohol Depend."},{"key":"B59","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/BF02805969","article-title":"Pharmacological Screen for Activities of 12-hydroxyibogamine: a Primary Metabolite of the Indole Alkaloid Ibogaine","volume":"127","author":"Staley","year":"1996","journal-title":"Psychopharmacology (Berl)"},{"key":"B60","doi-asserted-by":"publisher","first-page":"588","DOI":"10.2133\/dmpk.DMPK-10-RG-074","article-title":"PDZK1 Regulates Organic Anion Transporting Polypeptide Oatp1a in Mouse Small Intestine","volume":"25","author":"Sugiura","year":"2010","journal-title":"Drug Metab. Pharmacokinet."},{"key":"B61","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1007\/BF02245936","article-title":"Receptor Binding Profile Suggests Multiple Mechanisms of Action Are Responsible for Ibogaine's Putative Anti-Addictive Activity","volume":"118","author":"Sweetnam","year":"1995","journal-title":"Psychopharmacology (Berl)"},{"key":"B62","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1124\/mol.106.023556","article-title":"Functional Validation of the Genetic Polymorphisms of Human ATP-Binding Cassette (ABC) Transporter ABCG2: Identification of Alleles that Are Defective in Porphyrin Transport","volume":"70","author":"Tamura","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"4650","DOI":"10.1002\/jps.21771","article-title":"Ibogaine Labeling with 99mTc-Tricarbonyl: Synthesis and Transport at the Mouse Blood-Brain Barrier","volume":"98","author":"Tournier","year":"2009","journal-title":"J. Pharm. Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1017\/S1461145709990848","article-title":"Interaction of Drugs of Abuse and Maintenance Treatments with Human P-Glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2)","volume":"13","author":"Tournier","year":"2010","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.3390\/ijms22041935","article-title":"Identification of Two Dysfunctional Variants in the ABCG2 Urate Transporter Associated with Pediatric-Onset of Familial Hyperuricemia and Early-Onset Gout","volume":"22","author":"Toyoda","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1124\/dmd.108.024315","article-title":"Methotrexate Pharmacokinetics in Transgenic Mice with Liver-specific Expression of Human Organic Anion-Transporting Polypeptide 1B1 (SLCO1B1)","volume":"37","author":"van de Steeg","year":"2009","journal-title":"Drug Metab. Dispos."},{"key":"B67","doi-asserted-by":"publisher","first-page":"2942","DOI":"10.1172\/JCI42168","article-title":"Organic Anion Transporting Polypeptide 1a\/1b-Knockout Mice Provide Insights into Hepatic Handling of Bilirubin, Bile Acids, and Drugs","volume":"120","author":"van de Steeg","year":"2010","journal-title":"J. Clin. Invest."},{"key":"B68","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1158\/1078-0432.CCR-12-2080","article-title":"Influence of Human OATP1B1, OATP1B3, and OATP1A2 on the Pharmacokinetics of Methotrexate and Paclitaxel in Humanized Transgenic Mice","volume":"19","author":"van de Steeg","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"B69","doi-asserted-by":"publisher","first-page":"3583","DOI":"10.1172\/JCI33435","article-title":"Knockout of Cytochrome P450 3A Yields New Mouse Models for Understanding Xenobiotic Metabolism","volume":"117","author":"van Herwaarden","year":"2007","journal-title":"J. Clin. Invest."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1124\/mol.107.043869","article-title":"Midazolam Metabolism in Cytochrome P450 3A Knockout Mice Can Be Attributed to Up-Regulated CYP2C Enzymes","volume":"73","author":"van Waterschoot","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1021\/acschemneuro.8b00294","article-title":"DARK Classics in Chemical Neuroscience: Ibogaine","volume":"9","author":"Wasko","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"B72","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.cmpb.2010.01.007","article-title":"PKSolver: An Add-In Program for Pharmacokinetic and Pharmacodynamic Data Analysis in Microsoft Excel","volume":"99","author":"Zhang","year":"2010","journal-title":"Comput. Methods Programs Biomed."},{"key":"B73","doi-asserted-by":"publisher","first-page":"689","DOI":"10.2165\/11318030-000000000-00000","article-title":"Polymorphism of Human Cytochrome P450 2D6 and its Clinical Significance: Part I","volume":"48","author":"Zhou","year":"2009","journal-title":"Clin. Pharmacokinet."},{"key":"B74","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/S0893-133X(99)00003-2","article-title":"Noribogaine Generalization to the Ibogaine Stimulus: Correlation with Noribogaine Concentration in Rat Brain","volume":"21","author":"Zubaran","year":"1999","journal-title":"Neuropsychopharmacology"},{"key":"B75","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1111\/j.1527-3458.2000.tb00149.x","article-title":"Ibogaine and Noribogaine: Comparing Parent Compound to Metabolite","volume":"6","author":"Zubaran","year":"2000","journal-title":"CNS Drug Rev."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.855000\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T09:58:14Z","timestamp":1646387894000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.855000\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,4]]},"references-count":75,"alternative-id":["10.3389\/fphar.2022.855000"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.855000","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,4]]},"article-number":"855000"}}