Dear List,Back to the Top
We are seeing dramatically altered PK (increased T1/2, Cmax, AUC,
bioavailability, for example the Cmax is increased by >40X) of a
compound in diabetic (db/db) mice versus normal mice and rats. Is this
a common problem with diabetic models? Is anyone aware of any
precedent for this with other drugs? How about in humans?
Kevin P. Foley, Ph.D.
Principal Scientist, In Vivo Biology
Synta Pharmaceuticals Corp.
45 Hartwell Avenue
Lexington, MA 02421 USA
KevinBack to the Top
You can take a look at the paper: "Dynamic and kinetic disposition of
nisoldipine enantiomers in hypertensive patients presenting with type-2
Eur J Clin Pharmacol. 2002 Dec;58(9):607-14.
Hope this helps,
Paula Macedo Cerqueira, PhD
Pharmacist- Technical Consultant
Nacional Health Surveillance Agency - ANVISA
Bioequivalence Unity - S\0x201Eo Paulo -SP- Brazil
I am more aware of decreased parameters in diabetic animals, less ofBack to the Top
increased AUC and C max, diabetic animals are typically polyphagic and
polydypsic (increased food and water consumption) and affected by
polyuria (increased urine output), also the volume of distribution can
be affected such as in animals with obese phenotype (ob/ob diabetic
mouse). There is multiple report of drug with negatively affected
kinetics in diabetic animals (morphine, IGF). Check these paper which
might shed some light on this issue.
Biopharmacopae Design International
Dear Dr. Foley,Back to the Top
the work by Nelson & Brown in the late '80s and early '90s reports
significant differences in pk parameters between diabetic and normal
dogs. I do not have the reference handy. Let me know if you need more
and I will try and dig it up.
Rob Hunter, MS, PhD
Assistant Professor of Veterinary Pharmacology
Zoological & Analytical Pharmacology Laboratory
Department of Anatomy & Physiology
129 Coles Hall
College of Veterinary Medicine
Kansas State University
Manhattan, Kansas 66506-5802
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