kinetic question

[nikei3ball]

i have a question in a kinetics class, a drug has 90% bioavailability and linear pharmacokinetics. what benefits do these present? (i.e. is it just easy titration? also does that good bioavailability means that no adjusment necessary in renal impairment?)

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[Krismeese]

Hmm, well just from that information you have given. I don't think you can say anything specifically about dose adjustment requirements for renal impairment. In order to determine that you would need to know the fraction of drug excreted unchanged in the urine to be able to distinguish the relative importance of hepatic and renal clearance of the drug.

That being said, some things you can say is that if the elimination phase is linear you can use a two-point calculation to determine the elimination rate constant (and half-life) for that specific patient very easily. In a drug that you do not monitor blood levels, it probably also means that you can more safely use the half-lives published in the literature and tertiary sources to predict concentrations or times to steady state (important in determining such things as time to onset).

With regards to the 90% (assuming oral) bioavailability you can assume the drug is absorbed well in the gut, and consequently is a low extraction drug, and assuming the drug is mainly hepatically cleared, CYP enzyme induction/inhibition are important to consider, but you do not need to worry much about protein displacement.

I am just a student, but these are the things I think about when I read your question

 

[Priapism321]

i have a question in a kinetics class, a drug has 90% bioavailability and linear pharmacokinetics. what benefits do these present? (i.e. is it just easy titration? also does that good bioavailability means that no adjusment necessary in renal impairment?)

Why would good bioavailability translate to no dose adjustment in the setting of renal impairment? What would make you think this?

 

[nikei3ball]

thank you very much, its good

 

[Aznfarmerboi]

i have a question in a kinetics class, a drug has 90% bioavailability and linear pharmacokinetics. what benefits do these present? (i.e. is it just easy titration? also does that good bioavailability means that no adjusment necessary in renal impairment?)

It depends what linear pharmcokinetics you are looking at, but more or less it just translates to easier IV to PO dosing imo. Maybe SDN can help you better in this. . .

 

[pharmacogenomic]

It depends what linear pharmcokinetics you are looking at, but more or less it just translates to easier IV to PO dosing imo. Maybe SDN can help you better in this. . .

sdn can no longer log in - who knows why???

However, I'll give you what sdn would say

Krismeese had lots of good info. 90% bioavailabilty just means 90% of the oral dose is absorbed into the blood. That just addresses the various ways the drug might be extracted before it gets into the blood - from first pass thru the liver, degradation by stomach enzymes or pH (since most absorption is in the intestine), etc. It can sometimes be used to compare the dosing, as someone posted, between IV/po conversions.

Linear pharmacokinetics is a difficult term & a bit obtuse. I'm thinking they are meaning it is following a one compartment model. That means that the half-life is linear - with each half life, one-half of the drug in the blood is removed. In its most simplistic understanding - it normally takes 5 half lives for a drug to be removed.

It does not address the metabolic pathway at all. That can involve the kidney, liver or enzymes in the blood. It also does not address the target organ, disposition from the blood into the target organ, distribution or elimination half lives, etc..

Your question is really vague & you need to have greater & deeper understanding of pharmacokinetics to really understand how these terms relate to a real situation.

I'd recommend a good textbook on kinetics. Don't move forward until you understand what you've been assigned, so come back with more detail if you need. Take your time & go back over & over until you "get it".

Good luck - don't give up & really learn this well - it will be important for you later!

 

[npage148]

Linear Pk means that the clearance does not change with dose (the terminal disposition phase has a constant straight line slope. The number of compartments that model has doesn't ditcate whether it's linear or not. The simpliest is a one compartment model. It makes dose adjustment easier if your goal is a target plasma concetration. But, Linear PK doesnt mean that Pharmacodynamics are linear.

 

[pharmacogenomic]

Linear Pk means that the clearance does not change with dose (the terminal disposition phase has a constant straight line slope. The number of compartments that model has doesn't ditcate whether it's linear or not. The simpliest is a one compartment model. It makes dose adjustment easier if your goal is a target plasma concetration. But, Linear PK doesnt mean that Pharmacodynamics are linear.

Very true npage!!! However, it is only true when referring to the terminal disposition of the parent drug. It does not address either the metabolites nor the terminal disposition of the parent or the metabolites from end blood nor terminal tissue. When you have two or three compartments, you you must adjust for the kinetics of disposition & elimination of all compartments at the same time, which even if the parent drug & its metabolites are linear, the final consideration of the total blood level is not. I'm trying to think of a po drug, having 90% bioavailability,with a simple one compartment linear kinetics & can't think of one right now.....too tired! Npage - can you think of one where you are looking for a target blood level with simple linear disposition kinetics? Perhaps magnesium - but not po - only IV. I'm not clear if these were 2 separate questions or questions related. An example would help.

One thing we also missed is there is a difference between the pharmacokinetics of the actual drug & the pharmacokinetics of the therapeutic activity. SSRIs are good examples of the inability to follow blood level & get any idea of dosing. But, we can predict their pharmacodynamics pretty well. Npage made this point well with regard to those drugs in which we do follow blood level - the dynamics are often the more important factor & kinetics are a part of that, but they are not equal.

Thats why linear pk is currently a vague term - & why npage made the point that it doesn't reflect the pharmacodynamics at all.

 

[tussionex]

sdn can no longer log in - who knows why???

However, I'll give you what sdn would say

did she exceed the maximum number of posts allowed? or the maximum number of words per post?