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

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Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.creatorCosta, Ana Carolina Conchon-
Autor(es): dc.creatorde Lima Benzi, Jhohann Richard-
Autor(es): dc.creatorYamamoto, Priscila Akemi [UNESP]-
Autor(es): dc.creatorde Freitas, Maria Cristina Foss-
Autor(es): dc.creatorde Paula, Francisco José Albuquerque-
Autor(es): dc.creatorZanelli, Cleslei Fernando [UNESP]-
Autor(es): dc.creatorLauretti, Gabriela Rocha-
Autor(es): dc.creatorde Moraes, Natália Valadares [UNESP]-
Data de aceite: dc.date.accessioned2022-02-22T00:44:15Z-
Data de disponibilização: dc.date.available2022-02-22T00:44:15Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-04-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1111/bcp.14594-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/205409-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/205409-
Descrição: dc.descriptionAims: 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.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences of Ribeirão Preto USP – University of São Paulo-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences UNESP – São Paulo State University-
Descrição: dc.descriptionSchool of Medicine of Ribeirão Preto USP – University of São Paulo-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences UNESP – São Paulo State University-
Descrição: dc.descriptionCNPq: 142247/2014-6-
Descrição: dc.descriptionCNPq: 290076/2017-0-
Descrição: dc.descriptionCAPES: Finance Code 001-
Formato: dc.format1981-1989-
Idioma: dc.languageen-
Relação: dc.relationBritish Journal of Clinical Pharmacology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectgabapentin-
Palavras-chave: dc.subjectpopulation pharmacokinetics-
Palavras-chave: dc.subjecttype 2 diabetes-
Título: dc.titlePopulation pharmacokinetics of gabapentin in patients with neuropathic pain: Lack of effect of diabetes or glycaemic control-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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