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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The role of organic cation transporter 2 inhibitor cimetidine, experimental diabetes mellitus and metformin on gabapentin pharmacokinetics in rats

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de Lima Benzi, Jhohann Richard [1] ; Yamamoto, Priscila Akemi [2] ; Stevens, Jessica Hanna [2] ; Baviera, Amanda Martins [3] ; de Moraes, Natalia Valadares [2]
Total Authors: 5
[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Ribeirao Preto, SP - Brazil
[2] Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Principios Ativos Nat & Toxicol, Araraquara, SP - Brazil
[3] Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Anal Clin, Araraquara, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Life Sciences; v. 200, p. 63-68, MAY 1 2018.
Web of Science Citations: 1

Purpose: We investigated the influence of diabetes mellitus (DM), glycemic control with insulin, cimetidine (Oct2 inhibitor) and metformin (Oct2 substrate) on the kinetic disposition of GAB in rats. Main methods: Male Wistar rats were divided in five groups and all animals received an oral dose of 50 mg/kg GAB: (vehicle + GAB), cimetidine + GAB (single dose of cimetidine {[}100 mg/kg] intraperitoneally 1 h before GAB), metformin + GAB (single dose of metformin 100 mg/kg by gavage concomitantly with GAB), DM + GAB (single dose of 40 mg/kg streptozotocin (STZ) intravenously) and DM + GAB + insulin (single dose 40 mg/kg STZ intravenously and 2 IU insulin twice daily for 15 days). Pharmacokinetic analysis was based on plasma and urine data concentrations. Key findings: No differences in pharmacokinetic parameters were observed between vehicle + GAB x cimetidine + GAB and vehicle + GAB x metformin + GAB groups. Diabetes increased the fraction of GAB excreted unchanged in urine (vehicle+GAB: 0.48 {[}0.38-0.58]; DM + GAB: 0.83 {[}0.62-1.04]; DM + GAB + insulin: 0.88 {[}0.77-0.93]) (mean {[}95% confidence interval]) without any changes in GAB exposure. Insulin treated diabetic animals showed higher renal clearance compared to control (vehicle + GAB: 0.25 {[}0.18-0.30] L/; DM + GAB + insulin: 0.55 {[}0.45-1.43] L/, which was attributed to the diabetes-induced glomerular hyperfiltration. (AU)

FAPESP's process: 15/25728-2 - Influence of the organic cation transporter 2 (OCT2) inhibitor cimetidine and experimental diabetes mellitus on kinetic disposition of gabapentin in rats
Grantee:Jhohann Richard de Lima Benzi
Support type: Scholarships in Brazil - Master