The influence of metformin transporter gene SLC22A1 and SLC47A1 variants on steady-state pharmacokinetics and glycemic response
Penulis/Author
VITARANI D.A NINGRUM (1); dr. Ahmad Hamim Sadewa, Ph.D. (2); Prof. Dr. apt. Zullies Ikawati. (3); Rika Yuliwulandari (4); dr. Mohammad Robikhul Ikhsan, Sp.PD., K-EMD., M.Kes. (5); Rohmatul Fajriyah (6)
Tanggal/Date
29 2022
Kata Kunci/Keyword
Abstrak/Abstract
Interindividual variation is important in the response to metformin as the first-line therapy for
type-2 diabetes mellitus (T2DM). Considering that OCT1 and MATE1 transporters deter-
mine the metformin pharmacokinetics, this study aimed to investigate the influence of
SLC22A1 and SLC47A1 variants on the steady-state pharmacokinetics of metformin and
the glycemic response. This research used the prospective-cohort study design for 81
patients with T2DM who received 500 mg metformin twice a day from six primary healthcare
centers. SLC22A1 rs628031 A>G (Met408Val) and Met420del genetic variants in OCT1 as
well as SLC47A1 rs2289669 G>A genetic variant in MATE1 were examined through the
PCR-RFLP method. The bioanalysis of plasma metformin was performed in the validated
reversed-phase HPLC-UV detector. The metformin steady-state concentration was mea-
sured for the trough concentration (Cssmin) and peak concentration (Cssmax). The pharma-
codynamic parameters of metformin use were the fasting blood glucose (FBG) and glycated
albumin (GA). Only SLC22A1 Met420del alongside estimated-glomerular filtration rate
(eGFR) affected both Cssmax and Cssmin with an extremely weak correlation. Meanwhile,
SLC47A1 rs2289669 and FBG were correlated. This study also found that there was no cor-
relation between the three SNPs studied and GA, so only eGFR and Cssmax influenced GA.
The average Cssmax in patients with the G allele of SLC22A1 Met408Val, reaching 1.35-fold
higher than those with the A allele, requires further studies with regard to metformin safe
dose in order to avoid exceeding the recommended therapeutic range
Rumpun Ilmu
Kimia
Bahasa Asli/Original Language
English
Level
Internasional
Status
Dokumen Karya
No
Judul
Tipe Dokumen
Aksi
1
Vitarani Dwi Anandda_The influence of metformin.pdf
[PAK] Full Dokumen
2
The influence of metformin transporter gene SLC22A1 and SLC47A1 variants on steady-state pharmacokinetics and glycemic response (1).pdf