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Dear All,
I am studying the pharmacokinetics of metformin.
A natural product extract when co-administered with metformin at
500mg/kg increases the bioavailability of metformin
The same extract when administered at a dose of 1gm decreases the
bioavailability of metformin.
Can anybody guide me about the possible mechanisms of the same.
with kind regards
amrutesh
[500 mg/kg versus 1 g or 1g/kg? Species? - db]
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Dear Amrutesh,
Metformin was a substrate of renal OATs. Some ingredients in herb
extract might inhibit the the renal tubular secretion of metformin
resulting in higher plasma exposure and decreased renal clearance.
two references involving human studies:
1. Br J Clin Pharmacol. 1987 May;23(5):545;
2. Drug Metabol Drug Interact. 2002;19(1):41;
However, It is useful to know the species in your study.
Hong Lu
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Dear, Hong
Thanks for that help,
I am studying drug interaction in wistar rats.
--
Ms Yogita Ghodke
Research Fellow
Interdisciplinary School of Health Sciences
University of Pune
Pune 411007
India
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The following message was posted to: PharmPK
Dear Amrutesh,
is so happens that also there seems to be a dependence on tissues
whether
OAT or OCT may be involved in metformin transport
See e.g.
Wang DS, Jonker JW, Kato Y, Kusuhara H, Schinkel AH, Sugiyama Y. Related
Articles, Links
Involvement of organic cation transporter 1 in hepatic and intestinal
distribution of metformin.
J Pharmacol Exp Ther. 2002 Aug;302(2):510-5.
Hope this helps
Hans
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The following message was posted to: PharmPK
Based on the structure of Metformin (w/ 5 nitrogens and two relevant
basic pKa values) I doubt that it is a substrate for an organic anion
transporter. However, it definitely is a substrate for organic cation
transporter according to this reference.
Mike
1: J Clin Pharmacol. 2006 Feb;46(2):157-63.Click here to read Links
Variability in renal clearance of substrates for renal
transporters in chinese subjects.
* Yin OQ,
* Tomlinson B,
* Chow MS.
School of Pharmacy, Faculty of Medicine, The Chinese University
of Hong Kong, Shatin, NT, Hong Kong.
The authors evaluated the inter- and intraindividual variability
in the renal clearance of substrates of organic anion transporters
(OAT) or organic cation transporters (OCT) using repeated drug
application procedures. Two OAT substrates (ampicillin and
cephalexin) and 2 OCT substrates (famotidine and metformin) were
selected. Each drug was administered orally twice to healthy
subjects, with sample sizes ranging from 12 to 28 (using
bioequivalent formulations of each drug). The inter-(delta(inter))
and intrasubject (delta(intra)) variances in renal clearance were
estimated based on analysis of variance, and the genetic contribution
(r(GC)) was calculated as (delta(inter - intra))/delta(inter). The
renal clearances of ampicillin, cephalexin, famotidine, and metformin
averaged 5.21 (range, 2.87-11.20), 3.01 (range, 1.50-3.82), 4.96
(range, 2.84-8.17), and 9.44 (range, 5.66-15.43) mL/min/kg, with mean
intraindividual coefficients of variation of 17.7%, 7.3%, 13.5%, and
9.0% and r(GC) values of 0.75, 0.89, 0.81, and 0.93, respectively.
These high r(GC) values suggest a potential significant genetic
contribution by the renal OATs and OCTs in Chinese subjects. Further
studies in a larger population are needed to confirm the importance
of these results as well as to identify specific genetic variants in
these transporters responsible for such variability.
* Michael B. Bolger, Ph.D.
* Chief Scientist
* Phone: 707-769-1895 or (661) 723-7723 x 301
* FAX: (661) 723-5524
* Simulations Plus, Inc.
* 42505 10th Street West
* Lancaster, CA 93534
* U.S.A.
* http://www.simulations-plus.com (AMEX: SLP)
* bolger.-at-.simulations-plus.com
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