{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:35:27Z","timestamp":1788381327978,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,12,12]],"date-time":"2020-12-12T00:00:00Z","timestamp":1607731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gabapentinoids are substrate of L\u2010type amino acid transporter 1 (LAT1) for distribution across the blood\u2010brain barrier. The present study aimed to evaluate the effect of LAT1 rs4240803 genetic polymorphism on the clinical efficacy and tolerability of gabapentinoids in Pakistani patients with neuropathic pain. Three\u2010hundred and ninety\u2010two patients were recruited, genotyped for SNP rs4240803, and followed up for eight weeks to evaluate the clinical response to gabapentinoids in terms of pain relief, inadequate response, and the emergence of adverse events. LAT1 rs4240803 GG, GA, and AA genotype frequency were 33.42%, 47.96% and 18.62%, respectively. Out of 392 patients, 323 responded to the treatment and 17.6% discontinued either due to insufficient response or intolerable adverse events (AEs). GA genotype was more frequent in non\u2010responder group (<jats:italic>P\u00a0<\/jats:italic>\u02c2\u00a00.001). Maximum pain responders (\u226550%) in combination with the lowest incidence of AEs were observed in the GG group, whereas partial responders belonged to GA genotype and with the highest frequency of somnolence (83.6%) and dizziness (69.9%). Overall, 72.5% patients with GA genotype experienced AEs (<jats:italic>P\u00a0<\/jats:italic>\u02c2\u00a00.001). In conclusion, clinical outcomes of gabapentinoids are influenced by LAT1 rs4240803 polymorphism and population pharmacogenetics should be considered to evaluate the maximum potential of gabapentinoids in the management of neuropathic pain.<\/jats:p>","DOI":"10.1111\/bcpt.13534","type":"journal-article","created":{"date-parts":[[2020,11,15]],"date-time":"2020-11-15T09:01:25Z","timestamp":1605430885000},"page":"503-510","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Influence of single nucleotide polymorphism of LAT1 on therapeutic response to gabapentinoids in Pakistani patients with neuropathic pain"],"prefix":"10.1111","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8977-9820","authenticated-orcid":false,"given":"Abida","family":"Shaheen","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Shifa College of Medicine Shifa Tameer\u2010e\u2010Millat University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Mahboob","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics Basic Medical Sciences Institute JPMC Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad","family":"Azam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Shifa College of Medicine Shifa Tameer\u2010e\u2010Millat University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moosa","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Shaheed Zulfiqar Ali Bhutto Medical University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman","family":"Ahmad Saleem","sequence":"additional","affiliation":[{"name":"Department of Pain Clinic Shifa International Hospital Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afrose","family":"Liaquat","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Shifa College of Medicine Shifa Tameer\u2010e\u2010Millat University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana","family":"Mumtaz","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine and Psychotherapy University Medical Center G\u04e7ttingen G\u04e7ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2165\/11536200-000000000-00000"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409066103"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2786151"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/2042098613505614"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-012-0006-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4997\/JRCPE.2017.402"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2008.06.015"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.03.022"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2018.00243"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-018-2532-0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.5582\/irdr.2015.01024"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.03.022"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.13080"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.11.013"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.294.3704"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.345.15224"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.35.6.652"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13059"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181de0e6d"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJWH.S142052"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.36303\/SAJAA.2019.25.4.2253"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-025300"},{"key":"e_1_2_8_24_1","first-page":"1","article-title":"Pregabalin Medication Use Evaluation in a Tertiary Care Hospital in Riyadh","volume":"6","author":"Aljuhanei ME","year":"2017","journal-title":"PRJPPS."},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-2105"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12791"},{"key":"e_1_2_8_27_1","first-page":"CD007938","article-title":"Gabapentin for chronic neuropathic pain in adults","volume":"6","author":"Wiffen PJ","year":"2017","journal-title":"Cochrane Database Syst Rev."},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.644"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-018-0946-6"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S63028"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3344\/kjp.2020.33.1.3"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13126"}],"container-title":["Basic &amp; 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