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The following message was posted to: PharmPK
Hi everyone,I would like to know the main elimination
route for metformin,and if it has any metabolite(s)
I also would like to know if Metformin
accumulate/cause lactic acidosis in patients with
chronic renal failure (let say creatinine clearence
between 30-50 ml/min).
If there any journal article(s)on this topic please
let me know.
Thank you in advance.
Best regards,
Amani Phillip.
Curtin University of Technology,
Perth,Western Australia.
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The following message was posted to: PharmPK
Dear Phillip,
The physicochemical properties of the metformin molecule (low MW,
positive
charge at physiologic pH) lead to its fast renal elimination with no
significant metabolism. In patients with chronic renal failure,
metformin is
expected to accumulate in the body and may lead to lactic acidosis (the
adverse effect that usually is not seen in patients with normal renal
function that receive metformin).
There are numerous publications that discuss the pharmacokinetic and
pharmacodynamic features of metformin. Here are some of them:
Bailey C, Path M and Turner M. (1996) Metformin. N Engl J Med 334:
574-579.
Scheen AJ. (1996) Clinical pharmacokinetics of metformin. Clin
Pharmacokinet
30: 359-71.
C.J. Dunn and D.H. Peters, Metformin. A review of its pharmacological
properties and therapeutic use in non-insulin-dependent diabetes
mellitus.
Drugs. 49(5) (1995) 721-49.
Best regards,
David.
David Stepensky, post-doc student
Department of Pharmaceutics, School of Pharmacy,
The Hebrew University of Jerusalem, P.O.B. 12065,
Jerusalem, 91120, Israel.
tel: +972-2-6757667 (w)
fax: +972-2-6757246
cellular phone: +972-55-349669
email: davids.-at-.md.huji.ac.il
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The following message was posted to: PharmPK
Hi everyone,
I would like to express my sincere thanks to David and
Murad for their help in my questions on Metformin.I
have read the articles which you recommended and found
to be very useful.
Among the contraindications of Metformin is renal
failure,(I'm interested in chronic renal failure).Is
it possible to make dosage adjustment (using
creatinine clearence,serum creatinine or lactate
levels?) in these patients in order to prevent
accumulation of metformin as well as reducing/controll
the incidences of lactic acidosis?
Please let me know if there is any useful journal
articles on this topic.
Thank you,
Best regards,
Amani Phillip,
Curtin University of Technology,
Perth,WA
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The following message was posted to: PharmPK
Dear Phillip,
It is reasonable that dosage adjustment using parameters related
to renal function should prevent accumulation of metformin in the body.
I'm
not aware of the clinical studies assessing this issue, and in all the
studies I've seen, impaired renal function is a classical exclusion
criteria
for metfomin treatment.
Please, note that the pharmacological effect of metformin is not
directly
related to the plasma levels or accumulation in the body. Dose
adjustment
may result in decrease in anti-hyperglycemic activity due to lower
exposure
of the pre-systemic sites of action to the drug. Please, read our papers
that studied the PK-PD relationships of metformin:
Stepensky, D., Friedman, M., Raz, I. and Hoffman, A.:
Pharmacokinetic-pharmacodynamic analysis of the glucose-lowering effect
of
metformin in diabetic rats reveals first pass pharmacodynamic effect.
Drug
Metab Dispos, 2002, 30(8) 861-8.
Stepensky, D., Friedman, M., Srour, W., Raz, I. and Hoffman, A.:
Preclinical
evaluation of pharmacokinetic-pharmacodynamic rationale for oral CR
metformin formulation. J Control Release. 2001, 71(1): 107-15.
Best regards,
David.
David Stepensky, post-doc student
Department of Pharmaceutics, School of Pharmacy,
The Hebrew University of Jerusalem, P.O.B. 12065,
Jerusalem, 91120, Israel.
tel: +972-2-6757667 (w)
fax: +972-2-6757246
cellular phone: +972-55-349669
email: davids.at.md.huji.ac.il
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