Does the intact nephron hypothesis provide a reasonable model for metformin dosing in chronic kidney disease?

Pradhan, Sudeep; Duffull, Stephen B.; Wilson, Luke C.; Kuan, Isabelle H. S.; Walker, Robert; Putt, Tracey; Schollum, John; Wright, Daniel F. B.

doi:10.1111/bcp.14919

Cited by 3 publications

(2 citation statements)

References 28 publications

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“…Even for drugs eliminated by tubular secretion, such as metformin, the relationships between metformin renal clearance rates and eGFR values are linear. [15] Other researchers have reported that the variability in cefepime trough concentrations are largely explained by eGFR [16,17]. Li A et al believe that individualized use of AMI based on renal function is necessary.…”

Section: Discussionmentioning

confidence: 99%

The eGFR parameter model helps predict blood drug concentration of amisulpride in patients with schizophrenia

Wang,

Qu,

Wang

2024

Preprint

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Objective This study aimed to examine inter-patient variability in amisulpride levels, using a multiple regression model with a dataset acquired from Chinese patients with schizophrenia. Methods Plasma concentrations of amisulpride (153 data from 128 patients) were analyzed by four-covariate model and eGFR model and were validated using goodness-of-fit and external prediction ability analyses. The amisulpride levels were detected by 2D-LC-UV system. Results The eGFR model adequately characterized amisulpride levels with adjusted R2 0.457. The dose and eGFR values significantly affected concentrations, as follows: amisulpride concentration = 838.561–9.169*eGFR + 1.273*dose. To remain below the laboratory alert level, recommended dose should remain below 300 mg/d, 500 mg/d, and 700 mg/d for patients with eGFR of 60 ml/min/1.73 m2, 90 ml/min/1.73 m2, and 120 ml/min/1.73 m2, respectively. Once and twice daily treatment regiments yielded comparable trough concentration values. Conclusion The eGFR model is simpler and more accurate in predicting the concentration of AMI, and provides an evaluation method for safe and individualized use of AMI.

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Section: Discussionmentioning

confidence: 99%

The eGFR parameter model helps predict blood drug concentration of amisulpride in patients with schizophrenia

Wang,

Qu,

Wang

2024

Preprint

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“…Whilst metformin is mainly eliminated by tubular secretion, the relationship between metformin renal clearance and eGFR metrics was recently found to be linear. 31 Therefore, this would support the development of a proportional dose reduction strategy based on GFR in patients with CKD. 32 Also, the evidence from a systematic review of 15 observational studies regarding the safety of metformin in people undergoing dialysis is inconclusive.…”

Section: Metforminmentioning

confidence: 94%

Metformin—‘BRAINS & AIMS’ pharmacological/prescribing principles of commonly prescribed (Top 100) drugs: Education and discussion

Koslover

Bruce

Patel

et al. 2023

Brit J Clinical Pharma

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We review pharmacological/prescribing principles relating to metformin according to our mnemonic framework: ‘BRAINS & AIMS’ (Benefits, Risks, Adverse Effects, Interactions, Necessary prophylaxis, Susceptibilities, Administering, Informing, Monitoring and Stopping): Benefits: Metformin's licensed uses: Type 2 diabetes mellitus (T2DM) treatment, reduction in risk or delay of onset. No clear evidence metformin influences patient‐important outcomes [Cochrane Review (2020) of 18 RCTs (n = 10 680)]. Risks: Inexpensive, essential WHO list drug; use contraindicated/not tolerated in 15%: for example, contraindication: lactic acidosis in renal impairment (eGFR <30 mL/min/1.73 m2). Adverse effects: Common gastrointestinal (GI) side effects are dose‐related and include abdominal pain, decreased appetite, diarrhoea (usually transient), nausea and vomiting, altered taste; vitamin B12 deficiency. Rare: acute metabolic acidosis (lactic acidosis/diabetic ketoacidosis). Interactions (pharmacokinetic) occur with drugs impairing renal function and hence metformin excretion, and drugs inhibiting organic cation transporter 1 or 2 (OCT1, OCT2), and/or multidrug and toxin extrusion protein 1 (MATE1/2‐K), such as cimetidine, ranolazine, trimethoprim and verapamil, and inducers such as rifampicin. The risk of hypoglycaemia may increase when metformin is used in combination with other medications for diabetes (pharmacodynamic interaction). Necessary prophylaxis: Detect/treat vitamin B12 deficiency. Susceptible groups: Elderly/renal/liver impairment (lactic acidosis); safe in pregnancy/breastfeeding. Administering: Initially 500 mg once daily (morning) with breakfast; titrate only after 1 week. Informing (relevant BRAINS & A(I)MS principles). Monitoring: Renal function beforehand, and 6–12 monthly, HbA1c 3–6 monthly until controlled. Serum vitamin B12 levels if deficiency is suspected/risk factors for. Stopping: Encourage patients to continue medication, unless deteriorating renal/liver function. Reasons for deprescribing: no harms from stopping suddenly.

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Modeling Metformin and Dapagliflozin Pharmacokinetics in Chronic Kidney Disease

Shahidehpour,

Rashid,

Askari

et al. 2024

AAPS J

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Does the intact nephron hypothesis provide a reasonable model for metformin dosing in chronic kidney disease?

Cited by 3 publications

References 28 publications

The eGFR parameter model helps predict blood drug concentration of amisulpride in patients with schizophrenia

The eGFR parameter model helps predict blood drug concentration of amisulpride in patients with schizophrenia

Metformin—‘BRAINS & AIMS’ pharmacological/prescribing principles of commonly prescribed (Top 100) drugs: Education and discussion

Modeling Metformin and Dapagliflozin Pharmacokinetics in Chronic Kidney Disease

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