help with pharmacokinetics/biopharmecutics

[TotalKayOs]

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i have a bunch of question for kinetics and any help i could get would be appriciated. unfortunetly my professor is terrible at teaching and the school has had numerous complaints about him every year for the past ten years but still refuses to do anything about it. first off when is the right time to use a recti-linear plot and a semi log plot? second, are first order models always decresing plasma concentration with respect to time? third, why is the graph of a first order process with rapid distribution, with extravacular administration a straight horizontal line when graphing dose with respect to fraction remaining at administration site? does anyone know any good web sites that maybe of help?
thanks.

 

[loo]

Hey--do you attend ACP? If so, who is the professor? Sounds like my experience with biopharm/clinical p-kinetics!!

 

[TotalKayOs]

no, i go to mcp (mass college of pharmacy).

 

[vixen]

hi mr.kayos,

i wish i i could help you out....you sound so smart and cute! 😉

 

[INevrLearn]

Unfortunately, I had the self-proclaimed "father of modern kinetics" Dr. Robert Notari for kinetics, so I can probably help you. (He probably wrote your book. And he doesn't mind reminding us of that on a daily basis.)

You can use a semi-log plot for a number of purposes. The visual mathematical difference between zero- and first-order processes can be determined by looking at plots of data. (zero-order data plotted on rectilinear paper will yield a straight line, whereas first-order data will not. If you take the non-straight-line data from a rectilinear plot and graph it on semi-log paper, first order data will yield a straight line.)

Also.... most kinetic problems you will deal with as a pharmacist will be first-order processes. (There are, of course, exceptions.) In general, if you're dealing with first order, make it easy on yourself and use the semi-log graph.

"Are first order processes always.....?" No.

The question about FrRemaining at the admin. site...... Never heard of such. I dunno.

Once you get out of the introductory series of Kinetics classes and into the clinical pharmacokinetics, you won't have to worry so much about the in-vitro crap that is taught initially. Clinical gets away from graphs and rules,and lets you use your judgement about PATIENTS using the math that you've learned.

Our ClinPK professor put together a really good website if you want to check it out.....

www.edserv.musc.edu/clinpk

Hope some of that is coherent... just got out of a pharmacology exam. Good luck!

Matt

 

[TotalKayOs]

thanks for your help. i ended up getting an 85 on my kinetics test, due in part to your help.

 

[INevrLearn]

No problem. Glad you did well.

 

[TotalKayOs]

i had to bring this thread back out becasue kinetics has again reared it's ugly head. my question naw has to do with the "feathered line", "method or residual", "curve stripping". what i don't understand is where it interesects the rising absorbtion phase of the graph. it originates at the intercept on the y axis and magically crosses the cuve. mym prof didn't so a great just of expaling it or where it came from he just drew it on the board one day and that this is it. any help would be great.

 

[lord999]

I wish there was a way to put up visuals. Oh well, I'll try to explain this the best I can.

I. Method of residuals
MAJOR ASSUMPTION: Ka > K
How to feather a curve:
1. In the curve, you see an ascending portion, an apex, and a descending portion of the curve.
2. Take the desecending portion of the curve and select three points that make an OK straight line.
3. Draw the line back to the y-axis. We'll call this line you 3-point line. Get the slope of this line.
4. Now here comes the hard part. We now need to get the intersecting line. You are going to take a ruler and place it vertically on the log paper. Start at X = 1. Subtract the Y-values and write them down. Plot the line and get that slope. This line is called the intersecting (or residual) line because it only crosses the curve at one point.

Example
The points on the 3-pt. line are (15,1); (14,2); (13,3). Your curve line is (4,1); (7,2); (8,3). Your intersecting line is (11,1); (7,2); (13,3).

5. Note where the lines intersect. If they intersect at the Y-axis, absorption begins immediately. In the above example, they actually intersect at time = 2. This is called LAG TIME. This means that the drug takes some time to begin absorption due to physiological barriers.

6. OK. You are pretty much done. In most drugs, the slope of the tri-point line is the elimination line (K), and the slope of the intersecting line is the absorption rate (Ka). You can figure out Cp from the definite integral of the rate equation (Subtract the lines).


Ia. "Flip-flop" kinetics of residuals
MAJOR ASSUMPTION: K > Ka
You really cannot tell whether the two curve lines that you've drawn before are Ka or K. With most drugs, the line that you draw initial (pick the three points) is the elimination line (k line). However, there are times when the elimination (K) is faster than the rate of absorption (Ka). In this case, that means the three-point line that you drew is the absorption line (Ka), and the intersection line is the elimination line (K).

How do you know this? Well, you can't with just the oral. You need the IV infusion K to determine whether your three-point line is actually the elimination.

Example:
Say that the three-point curve has a slope of 4. The intersecting line has a slope of 7. In this same patient, the IV infusion determined that K was 7. What is the rate of absorption? (4, because that is the line that is left.)

II. Wagner-Nelson (Du Percent Versus Time)
I'll post this if you want to.


For further reference, find a Schoenwald textbook. It's better than the POS Shargel and Yu.

 

[TotalKayOs]

holy crap. that helped a lot. it really did clear up a lot of my questions. thank you very much for the in depth and helpful information. i may try to find the text in a library for refrence. thanks again.

 

[pharmacychic01]

Hello. I am in my second year of pharmacy school and I am having a hard time with this pharmacokinetics/biopharmaceutics project. I am depsperate for help and I have a million questions. I would really appreciate any help. If anyone has a fax machine, I could fax a copy of questions. Thanks. 🙂

Unfortunately, I had the self-proclaimed "father of modern kinetics" Dr. Robert Notari for kinetics, so I can probably help you. (He probably wrote your book. And he doesn't mind reminding us of that on a daily basis.)

You can use a semi-log plot for a number of purposes. The visual mathematical difference between zero- and first-order processes can be determined by looking at plots of data. (zero-order data plotted on rectilinear paper will yield a straight line, whereas first-order data will not. If you take the non-straight-line data from a rectilinear plot and graph it on semi-log paper, first order data will yield a straight line.)

Also.... most kinetic problems you will deal with as a pharmacist will be first-order processes. (There are, of course, exceptions.) In general, if you're dealing with first order, make it easy on yourself and use the semi-log graph.

"Are first order processes always.....?" No.

The question about FrRemaining at the admin. site...... Never heard of such. I dunno.

Once you get out of the introductory series of Kinetics classes and into the clinical pharmacokinetics, you won't have to worry so much about the in-vitro crap that is taught initially. Clinical gets away from graphs and rules,and lets you use your judgement about PATIENTS using the math that you've learned.

Our ClinPK professor put together a really good website if you want to check it out.....

www.edserv.musc.edu/clinpk

Hope some of that is coherent... just got out of a pharmacology exam. Good luck!

Matt

 

[SummitPK]

PK Solutions is a commercial Excel-based pharmacokinetics data analysis software template that used polyexponetial curve-stripping and trapezoidal area methods to compute all important and widely used pk parameters.

The web site at http://www.SummitPK.com has lots of free and useful information on:

😀 curve fitting - see how it is done in the Tour and the User Guide (free downloads).

😀 AUC - same as above and try out the free PK Tutor download.

😀 PK Equations - a list of the whole shebang of pk equations calculated by polyexponential terns (from curve stripping) and area (AUC) methods - download a free pdf file or the interactive browser version.

As for curve-fitting, almost every pharmacokinetics text book (see a bibliography listing of about 12 of them in the PK Equations pdf or the PK Solutions User Guide) discusses and illustrates curve-stripping. But the two that excel at this are Gibaldi and Perrier (by far the best book ever if you want to be matehmatically literate in pharmacokinetics) and Notari. And PK Solutions Excels in doing it ... the easy way!

Pass this news on, and beware of academentia, because "easy, simple, direct, practical, economical, standard, normal, uncomplicated and understandable" are still admirable educational goals, teaching styles, and software attributes.

Keep cool, but don't freeze.

Cheers, SummitPK 👍