Disposition of Metformin (N, N-Dimethylbiguanide) in Man

Sirtori, C.R.; Galli, Giovanni; Cighetti, Giuliana; Galli-Kienle, M.; Franceschini, Guido

doi:10.1016/b978-0-08-023768-8.52522-6

Cited by 46 publications

(71 citation statements)

References 10 publications

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“…However, the direct correlation between metformin renal clearance and the ages of our subjects was weaker (r= 0.76) than that between metformin renal clearance and creatinine clearance (r= 0.85). Furthermore, Sirtori et al (1978) studied patients with more severe renal impairment than ours and their data support a strong correlation between metformin renal clearance and creatinine clearance (Figure 9b).…”

Section: Duicussonmentioning

confidence: 85%

“…Apart from the work reported here two other groups have studied the kinetics of metformin after intravenous administration to normal subjects (Sirtori et aL, 1978;Pentikainen etaaL, 1979). A comparison of the findings is summarized in Table 6.…”

Section: Duicussonmentioning

confidence: 99%

“…0306-5251/81/080235-12 $01.00 In spite of its widespread use, little is known about the pharmacokinetics of metformin. Two recent papers have described the kinetics in normal man (Sirtori et al, 1978;Pentikainen, Neuvonen & Penttila, 1979) and in one of these (Sirtori etal., 1978) special emphasis was placed upon the relationship between impairment of renal function and the resulting slowing of metformin clearance. The literature is deficient in information concerning the kinetics of metformin in patients with diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Metformin kinetics in healthy subjects and in patients with diabetes mellitus.

Tucker¹,

Casey²,

Phillips³

et al. 1981

Brit J Clinical Pharma

407

411

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Section: Duicussonmentioning

confidence: 85%

Section: Duicussonmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Metformin kinetics in healthy subjects and in patients with diabetes mellitus.

Tucker¹,

Casey²,

Phillips³

et al. 1981

Brit J Clinical Pharma

407

411

View full text Add to dashboard Cite

“…Drugs such as metformin are dependent on renal transporters for their ultimate urinary elimination. Interindividual variations in the renal secretion of metformin have been documented (Sirtori et al, 1978;Yin et al, 2006). Therefore, recent studies in healthy volunteers have investigated the effect of the c.808GϾT genotype on renal elimination of metformin (Song et al, 2008a;Wang et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of the Human Organic Cation Transporter 2 Variant p.270Ala>Ser

Zolk

Solbach²,

König³

et al. 2009

Drug Metabolism and Disposition

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ABSTRACT:The organic cation transporter 2 (OCT2, SLC22A2) plays an important role for renal drug elimination. Recent clinical studies indicate an impact of the frequent nonsynonymous c.808G>T (p.270Ala>Ser) polymorphism on renal clearance of metformin and the extent of the metformin-cimetidine interaction. The role of this polymorphism for renal disposition of endogenous compounds and drugs other than metformin has not been investigated. In addition, it is unclear whether the observed genotype dependence of an OCT2-mediated drug-drug interaction might occur also with other OCT inhibitors. To address these issues, we generated human embryonic kidney cells stably expressing wild-type OCT2 or the p.270Ala>Ser variant. No differences in protein expression levels and membrane incorporation pattern were observed between the two cell lines. The p.270Ala>Ser variant significantly impaired uptake kinetics of 1-methyl-4-phenylpyridinium, dopamine, norepinephrine, and propranolol. V max values were significantly reduced for uptake of all four compounds mediated by the p.270Ala>Ser variant compared with wild-type OCT2. In addition, a significant difference in the affinity to wild-type and mutant OCT2 was observed for dopamine (K m dopamine: 932 ؎ 77 versus 1285 ؎ 132 M). Moreover, out of a set of 27 compounds p.270Ala>Ser OCT2 was significantly less sensitive to inhibition by cimetidine, flurazepam, metformin, mexiletine, propranolol, and verapamil than wild-type OCT2 (e.g., for propranolol: IC 50 wild type versus p.270Ala>Ser 189 versus 895 M, P < 0.001). Our results indicate that the common OCT2 c.808G>T single nucleotide polymorphism significantly alters uptake of endogenous compounds and drugs. Moreover, for selected compounds the extent of OCT2-mediated drug interactions could depend on OCT2 c.808G>T genotype.

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“…Hashmi suggested that in published cases with metformin-induced hepatotoxicity the number of reported cases on this subject was underestimated, probably due to the lack of a consistent terminology [8]. Because metformin is not metabolized in the liver, it has been considered safe from a hepatic standpoint; however, metformin hepatotoxicity has rarely been reported [9,10]. Possible mechanisms of injury are direct, idiosyncratic, or a drug-drug interaction leading to acute hepatocellular and/or cholestatic jaundice [9,11].…”

Section: Discussionmentioning

confidence: 99%

A Rare Outcome Induced by Metformin Intoxication: Severe Lactic Acidosis and Hepatotoxicity

et al. 2016

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Metformin is a widely used oral anti-diabetic agent that decreases insulin resistance. Lactic acidosis rarely develops with this medication. Metformin-induced hepatotoxicity has been rarely reported in the literature. We describe a patient, who presented with lactic acidosis and hepatotoxicity after ingestion of 40 pills of metformin in order to commit suicide. The most important treatment step in patients with metformin-associated lactic acidosis (MALA) is high-volume hemodialysis and hemofiltration.

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Disposition of Metformin (N, N-Dimethylbiguanide) in Man

Cited by 46 publications

References 10 publications

Metformin kinetics in healthy subjects and in patients with diabetes mellitus.

Metformin kinetics in healthy subjects and in patients with diabetes mellitus.

Functional Characterization of the Human Organic Cation Transporter 2 Variant p.270Ala>Ser

A Rare Outcome Induced by Metformin Intoxication: Severe Lactic Acidosis and Hepatotoxicity

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