Back to the Top
We conducted a study in healthy volunteers where the drug of interest was given via an IV infusion q 12 hours. The drug was given for 21 days and intensive blood sampling was done on days 1, 3, 7, 14 and 21 days (all between 0-12 hours). In addition to collecting plasma samples, we also collected urine for 12 hours (0-4, 4-8, 8-12 hour collections) on those days. So we have a fairly rich dataset but unsure of what to do with it.
If I wish to determine the percent of administered dose excreted in the urine, I could just use the plasma and urine data from the first collection to determine that. What additional information would urine collected at steady state provide? Should I even do any analysis of urine samples on those days? From the analysis of urine data following the administration of the first dose, very little is excreted unchanged in the urine.
Thanks for your comments.
Back to the Top
The following message was posted to: PharmPK
Martin,
The amount of data you have should allow fitting an appropriate model with
GastroPlus. Let me know if you'd like to try it.
Best regards,
Walt
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (NASDAQ: SLP)
42505 10th Street West
Lancaster, CA 93534-7059
U.S.A.
http://www.simulations-plus.com
Back to the Top
On the last day, assuming steady state conditions have been established, you can determine urinary clearance from the equation amount excreted in the urine from 0-12hr/ AUC (0-12). Make sure units are the same eg., amount in ug and AUC in ugXhr/ml.
You can also determine steady state plasma clearance from the equation dose per dosing interval (0-12 hr)/AUC (0-12). One can then compare renal clearance of the drug vs plasma clearance and determine fraction of total clearance attributed to renal clearance.
If you know the protein binding then you can derive if there was tubular secretion/reabsorption or simple glomerular filtration.
Hope this is helful, Aziz Karim
Back to the Top
The following message was posted to: PharmPK
can you just elaborate or give an reference of using protein binding
data for deriving the tubular secretion/glomerular filtration?
Back to the Top
Vijaya Bhargava wrote:
Can you just elaborate or give an reference of using protein binding
data for deriving the tubular secretion/glomerular filtration?
Dear Dr Bhargava:
With reference to your above question, let me try to elaborate further:
When working with Renal Clearance (CLRen) issues, three physiologic parameters are important. These are:
1) Renal Blood Fow (RBF) =1200 ml/min
2) Glomelrular Filtration Rate (GFR) = 125 ml/min
3) Urine Flow = 1.5 ml/min.
Glomerular Filtration: Glomerular filtration is pssive removal of the drug from the blood as blood flows through the glomeruli of the kidney. If CLRen depends only on filtration then
CLRen = GFR * fu, where fu is the protein unbound fraction of the drug. Here the value of CLRenal of the drug would be approximately 120 ml/min, eg creatinine
Tubular Secretion: Tubular secretion can increase the CLRen by actively secreting the drug (usually transporters are involved). CLRen for drugs that may be maximally secreted would approach RBF which is about 1200 m/min, eg penicillin.
Rubular Reabsorption: Some drugs may be reabsorbed after being filtered out of the blood. Thus, the CLRen may be less than 120 ml/min (ie, GFR).If a drug is completely reabsobed after filtration and no active secretion occurs, then CLRenal of the drug will be limited to the amount of drug that leaves the kidney as the urine flows in to the bladder. So CLRen = (urine flow = 1.5 ml/min) * fu.
This is the reason why I stated that if one knows the protein binding of the drug, one can derive additional information.
Regards, Aziz Karim
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Urine data" as the subject | Support PharmPK by using the |
Copyright 1995-2011 David W. A. Bourne (david@boomer.org)