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In order to study whether pharmacogenetics explains some of the variability in the response to fentanyl, several genes related to fentanyl receptors, transporters and metabolic enzymes have been analysed. Thirty\u2010five healthy volunteers (19 men and 16 women) receiving a single 300 \u03bcg oral dose of fentanyl were genotyped for 9 polymorphisms in cytochrome P450 (CYP<\/jats:styled-content>) enzymes (CYP<\/jats:styled-content>3A4<\/jats:italic> and CYP<\/jats:styled-content>3A5)<\/jats:italic>, ATP<\/jats:styled-content>\u2010binding cassette subfamily B member 1 (ABCB<\/jats:styled-content>1)<\/jats:italic>, opioid receptor mu 1 (OPRM<\/jats:styled-content>1)<\/jats:italic>, catechol\u2010O\u2010methyltransferase (COMT<\/jats:styled-content>)<\/jats:italic> and adrenoceptor beta 2 (ADRB<\/jats:styled-content>2)<\/jats:italic> by real\u2010time PCR<\/jats:styled-content>. Fentanyl concentrations were measured by ultra\u2010performance liquid chromatography combined with tandem mass spectrometry (UPLC<\/jats:styled-content>\u2010MS<\/jats:styled-content>\/MS<\/jats:styled-content>). Fentanyl pharmacokinetics is affected by sex. Carriers of the CYP<\/jats:styled-content>3A4*22<\/jats:italic> allele,<\/jats:italic> which is known to reduce the mRNA<\/jats:styled-content> expression, showed higher area under the concentration\u2010time curve (AUC<\/jats:styled-content>) and lower clearance (Cl) values. Although this finding might be of importance, its validity needs to be confirmed in other similar settings. Furthermore, carriers of the ABCB<\/jats:styled-content>1<\/jats:italic> C1236T T\/T genotype presented a lower AUC<\/jats:styled-content> and higher Cl, as well as lower half\u2010life (T1\/2<\/jats:sub>). As volunteers were blocked with naltrexone, the effect of fentanyl on pharmacodynamics might be biased; however, we could observe that fentanyl had a hypotensive effect. Moreover, ADRB<\/jats:styled-content>2<\/jats:italic> C523A A allele carriers showed a tendency towards reducing systolic blood pressure. Likewise, OPRM<\/jats:styled-content>1<\/jats:italic> and COMT<\/jats:styled-content><\/jats:italic> minor allele variants were risk factors for the development of somnolence. CYP<\/jats:styled-content>3A5*3<\/jats:italic>, ABCB<\/jats:styled-content>1<\/jats:italic> C3435T and ABCB<\/jats:styled-content>1<\/jats:italic> G2677T\/A were not associated with fentanyl's pharmacokinetics, pharmacodynamics and safety profile.<\/jats:p>","DOI":"10.1111\/bcpt.13141","type":"journal-article","created":{"date-parts":[[2018,10,5]],"date-time":"2018-10-05T15:36:29Z","timestamp":1538753789000},"page":"321-329","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Polymorphisms associated with fentanyl pharmacokinetics, pharmacodynamics and adverse effects"],"prefix":"10.1111","volume":"124","author":[{"given":"Miriam","family":"Saiz\u2010Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Madrid 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Belmonte","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Plataforma SCReN (Spanish Clinical Research Network) UICEC Hospital Universitario de La Princesa Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Plataforma SCReN (Spanish Clinical Research Network) UICEC Hospital Universitario de La Princesa Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Alday","sequence":"additional","affiliation":[{"name":"Anesthesiology Department Instituto de Investigaci\u00f3n Sanitaria la Princesa (IP) Hospital Universitario de La Princesa Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Koller","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Zubiaur","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Mej\u00eda","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Plataforma SCReN (Spanish Clinical Research Network) UICEC Hospital Universitario de La Princesa Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Hern\u00e1ndez\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP) Universidad Aut\u00f3noma de Madrid (UAM) Madrid 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