Population pharmacokinetics of gabapentin in patients with neuropathic pain: Lack of effect of diabetes or glycaemic control

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dc.contributor.authorCosta, Ana Carolina Conchon
dc.contributor.authorde Lima Benzi, Jhohann Richard
dc.contributor.authorYamamoto, Priscila Akemi [UNESP]
dc.contributor.authorde Freitas, Maria Cristina Foss
dc.contributor.authorde Paula, Francisco José Albuquerque
dc.contributor.authorZanelli, Cleslei Fernando [UNESP]
dc.contributor.authorLauretti, Gabriela Rocha
dc.contributor.authorde Moraes, Natália Valadares [UNESP]
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2021-06-25T10:14:51Z
dc.date.available2021-06-25T10:14:51Z
dc.date.issued2021-04-01
dc.description.abstractAims: 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. Methods: A clinical trial was conducted in patients with neuropathic pain (n = 29) due to type 2 diabetes (n = 19) or lumbar/cervical disc herniation (n = 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 SLC22A2 (rs316019) and SLC22A4 (rs1050152), the genes encoding the transporters for organic cations OCT2 and OCTN1, were tested as potential covariates. Results: GBP drug disposition was described by a 1-compartment model with lag-time, first-order absorption and linear elimination. The total clearance was dependent on estimated glomerular filtration rate. Population estimates (between-subject variability in percentage) for lag time, first-order absorption rate, apparent volume of distribution and total clearance were 0.316 h (10.6%), 1.12 h−1 (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, SLC22A2 or SLC22A4 genotypes. Conclusion: 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.en
dc.description.affiliationSchool of Pharmaceutical Sciences of Ribeirão Preto USP – University of São Paulo
dc.description.affiliationSchool of Pharmaceutical Sciences UNESP – São Paulo State University
dc.description.affiliationSchool of Medicine of Ribeirão Preto USP – University of São Paulo
dc.description.affiliationUnespSchool of Pharmaceutical Sciences UNESP – São Paulo State University
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdCNPq: 142247/2014-6
dc.description.sponsorshipIdCNPq: 290076/2017-0
dc.description.sponsorshipIdCAPES: Finance Code 001
dc.format.extent1981-1989
dc.identifierhttp://dx.doi.org/10.1111/bcp.14594
dc.identifier.citationBritish Journal of Clinical Pharmacology, v. 87, n. 4, p. 1981-1989, 2021.
dc.identifier.doi10.1111/bcp.14594
dc.identifier.issn1365-2125
dc.identifier.issn0306-5251
dc.identifier.lattes1525665408900195
dc.identifier.orcid0000-0001-7831-1149
dc.identifier.scopus2-s2.0-85094645070
dc.identifier.urihttp://hdl.handle.net/11449/205409
dc.language.isoeng
dc.relation.ispartofBritish Journal of Clinical Pharmacology
dc.sourceScopus
dc.subjectgabapentin
dc.subjectpopulation pharmacokinetics
dc.subjecttype 2 diabetes
dc.titlePopulation pharmacokinetics of gabapentin in patients with neuropathic pain: Lack of effect of diabetes or glycaemic controlen
dc.typeArtigo
unesp.author.lattes1525665408900195[6]
unesp.author.orcid0000-0002-9955-0699[1]
unesp.author.orcid0000-0002-4389-058X[8]
unesp.author.orcid0000-0001-7831-1149[6]

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