{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:52:10Z","timestamp":1773337930383,"version":"3.50.1"},"reference-count":77,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["142247\/2014\u20106"],"award-info":[{"award-number":["142247\/2014\u20106"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["290076\/2017\u20100"],"award-info":[{"award-number":["290076\/2017\u20100"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["Finance Code 001"],"award-info":[{"award-number":["Finance Code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Gabapentin (GBP) is widely used to treat neuropathic pain, including diabetic neuropathic pain. Our objective was to evaluate the role of diabetes and glycaemic control on GBP population pharmacokinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A clinical trial was conducted in patients with neuropathic pain (<jats:italic>n<\/jats:italic> = 29) due to type 2 diabetes (<jats:italic>n<\/jats:italic> = 19) or lumbar\/cervical disc herniation (<jats:italic>n<\/jats:italic> = 10). All participants were treated with a single oral dose GBP. Blood was sampled up to 24 hours after GBP administration. Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm. Weight, body mass index, sex, biomarkers of renal function and diabetes, and genotypes for the main genetic polymorphisms of <jats:italic>SLC22A2<\/jats:italic> (rs316019) and <jats:italic>SLC22A4<\/jats:italic> (rs1050152), the genes encoding the transporters for organic cations OCT2 and OCTN1, were tested as potential covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GBP drug disposition was described by a 1\u2010compartment model with lag\u2010time, first\u2010order absorption and linear elimination. The total clearance was dependent on estimated glomerular filtration rate. Population estimates (between\u2010subject variability in percentage) for lag time, first\u2010order absorption rate, apparent volume of distribution and total clearance were 0.316 h (10.6%), 1.12 h<jats:sup>\u22121<\/jats:sup> (10.7%), 140 L (7.7%) and 14.7 L\/h (6.97%), respectively. No significant association was observed with hyperglycaemia, glycated haemoglobin, diabetes diagnosis, age, sex, weight, body mass index, <jats:italic>SLC22A2<\/jats:italic> or <jats:italic>SLC22A4<\/jats:italic> genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This population pharmacokinetics model accurately estimated GBP concentrations in patients with neuropathic pain, using estimated glomerular filtrationrate as a covariate for total clearance. The distribution and excretion processes of GBP were not affected by hyperglycaemia or diabetes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14594","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T02:51:33Z","timestamp":1603939893000},"page":"1981-1989","source":"Crossref","is-referenced-by-count":11,"title":["Population pharmacokinetics of gabapentin in patients with neuropathic pain: Lack of effect of diabetes or glycaemic control"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-0699","authenticated-orcid":false,"given":"Ana Carolina Conchon","family":"Costa","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto USP \u2013 University of S\u00e3o Paulo  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jhohann Richard","family":"de Lima Benzi","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto USP \u2013 University of S\u00e3o Paulo  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscila Akemi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto USP \u2013 University of S\u00e3o Paulo  Ribeir\u00e3o Preto SP Brazil"},{"name":"School of Pharmaceutical Sciences UNESP \u2013 S\u00e3o Paulo State University  Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina Foss","family":"de Freitas","sequence":"additional","affiliation":[{"name":"School of Medicine of Ribeir\u00e3o Preto USP \u2013 University of S\u00e3o Paulo  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco Jos\u00e9 Albuquerque","family":"de Paula","sequence":"additional","affiliation":[{"name":"School of Medicine of Ribeir\u00e3o Preto USP \u2013 University of S\u00e3o Paulo  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cleslei Fernando","family":"Zanelli","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences UNESP \u2013 S\u00e3o Paulo State University  Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela Rocha","family":"Lauretti","sequence":"additional","affiliation":[{"name":"School of Medicine of Ribeir\u00e3o Preto USP \u2013 University of S\u00e3o Paulo  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-058X","authenticated-orcid":false,"given":"Nat\u00e1lia Valadares","family":"de Moraes","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences UNESP \u2013 S\u00e3o Paulo State University  Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1989.tb03401.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.302"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03261926"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0773.2002.900402.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.070672"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-004-0678-9"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/187231208783478425"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.188"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01270.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2012.05.005"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.04.014"},{"issue":"2","key":"e_1_2_10_13_1","first-page":"233","article-title":"Effect of diabetes mellitus on the metabolism of drugs and toxins","volume":"5","author":"Vahabzadeh M","year":"2015","journal-title":"J Clin Toxicol"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20133257"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0738"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S9089"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2012.09.003"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2015.12.018"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-S002"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2008.080246"},{"issue":"1","key":"e_1_2_10_21_1","first-page":"28","article-title":"Delayed gastric emptying is related to cardiovascular autonomic neuropathy in Chinese patients with type 2 diabetes","volume":"74","author":"Bian RW","year":"2011","journal-title":"Acta Gastroenterol Belg"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12255"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01383-18"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.2000.02076.x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/894087","article-title":"Decreased gastric motility in type II diabetic patients","volume":"2014","author":"Chiu YC","year":"2014","journal-title":"Biomed Res Int"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016060666"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.22.6.982"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912700122012760"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200013338676"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/meta.2000.17721"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136390"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2012.06.013"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.10.009"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.280.21.1831"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(02)00255-5"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70251-0"},{"key":"e_1_2_10_37_1","unstructured":"KammermanPR FinnerupNB deLimaL HaroutounianS RajaSN RiceAS.Gabapentin for neuropathic pain: an application to the 21st meeting of the WHO Expert Committee on Selection and Use of Essential Medicines for the inclusion of gabapentin on the WHO Model List of Essential Medicines.2016.https:\/\/doi.org\/10.6084\/m9figshare.3814206.v2http:\/\/www.who.int\/selection_medicines\/committees\/expert\/21\/applications\/s2_gabapentin.pdfAccessed July 7 2017."},{"key":"e_1_2_10_38_1","first-page":"1","article-title":"Gabapentin add\u2010on for drug\u2010resistant focal epilepsy","volume":"10","author":"Panebianco M","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb00743.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13802"},{"issue":"6","key":"e_1_2_10_41_1","first-page":"S17","article-title":"Clinical pharmacokinetics of gabapentin","volume":"44","author":"Mclean MJ","year":"1994","journal-title":"Neurology"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb00932.x"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100271"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03616.x"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp400295c"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1603"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000282763.29778.59"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2009.04.005"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-150-9-200905050-00006"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13126"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.131"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2012.4"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.14"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12161"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00006.x"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1994.118"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2009.09.030"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2011.12.004"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S130942"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012412908983"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.03.012"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00582.2011"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.5455\/ijmsph.2016.11072015192"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1839809"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573399810666140606103645"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2001-0039"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004110970"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0135-z"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2005.12.302"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.147918"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(01)00311-4"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270012439209"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e318194767d"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.28.19738"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-005-0221-x"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2008.06.015"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9111-6"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-9155-6"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14594","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.14594","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14594","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T05:53:56Z","timestamp":1693288436000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.14594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":77,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1111\/bcp.14594"],"URL":"https:\/\/doi.org\/10.1111\/bcp.14594","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11]]}}}