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#1
03-30-2012
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Difference between rate of elimination and clearance?

Which statement is accurate for the drug shown in the example below?
100 mg 2hr -» 50 mg 2hr -> 25 mg 2 h r -» 12.5 mg
A. The rate of elimination is constant
B. The elimination half-life varies with the dose
C. The volume of distribution varies with the dose
D. The clearance varies with the dose
E. The rate of elimination varies directly with the dose

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#2
04-03-2012
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A

The rate of elimination is constant - A it is.
#3
04-04-2012
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#4
04-04-2012
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No its not E

its A.
Rate is constant, 50% is eliminated. Its First Order kinetics.
I feel like Kaplan Biobchem after-chapter questions are poorly written
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#5
04-04-2012
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Kaplan says this

Quote:
 Originally Posted by DocSikorski No its not E its A. Rate is constant, 50% is eliminated. Its First Order kinetics. I feel like Kaplan Biobchem after-chapter questions are poorly written
Its from pharma

Answer E. In first-order kinetics, the elimination rate of a drug is directly proportional to its plasma concentration, which in turn is proportional to the dose. Drugs that follow first-order elimination have a constant elimination half-life similar to the example given in the question. Likewise, clearance and volume of distribution are pharmacokinetic characteristics of a drug that do not routinely change with dose, although they may vary in terms of disease or dysfu.netion.
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#6
04-04-2012
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Quote:
 Originally Posted by DocSikorski No its not E its A. Rate is constant, 50% is eliminated. Its First Order kinetics. I feel like Kaplan Biobchem after-chapter questions are poorly written

I totally agree with DocSikorski. Actually I had a similar problem with that question at the end of the General Principles in Pharm. Rate=fraction -> here rate is constant - it's 50%. As DocSikorski pointed out it's First Order Kinetics, with T1/2 =2 hrs.
It's the amount of the eliminated drug what is proportional to plasma level, not the rate as they say in answer E). If we give 100 mg after 1 x T1/2 we'll have 50 mg. If we give 50 mg of the same drug after 1 x T1/2 we'll have 25 mg. So the rate remains constant (50%), it's the eliminated amount what changes and is proportional to plasma level/administered dose (the higher the dose, the more we loose after T1/2).

If anyone can see any incorrectness in this logic pleeeease let me know!
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#7
04-04-2012
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Quote:
 Originally Posted by Casandra I totally agree with DocSikorski. Actually I had a similar problem with that question at the end of the General Principles in Pharm. Rate=fraction -> here rate is constant - it's 50%. As DocSikorski pointed out it's First Order Kinetics, with T1/2 =2 hrs. It's the amount of the eliminated drug what is proportional to plasma level, not the rate as they say in answer E). If we give 100 mg after 1 x T1/2 we'll have 50 mg. If we give 50 mg of the same drug after 1 x T1/2 we'll have 25 mg. So the rate remains constant (50%), it's the eliminated amount what changes and is proportional to plasma level/administered dose (the higher the dose, the more we loose after T1/2). If anyone can see any incorrectness in this logic pleeeease let me know!
I know its stupid but can you please explain the difffrence b/w clearance and rate of elimination?

Also rate of elimination = coc/time
Which keep changing with every half life ?

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#8
04-04-2012
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[QUOTE=Kabutar111;108662]I know its stupid but can you please explain the difffrence b/w clearance and rate of elimination?

Also rate of elimination = coc/time
Which keep changing with every half life ?

Stupid question? Wait till you see some of mines in this forum I have like tonz of them!

I’ll try to explain. Please don’t be harsh on me if I don’t succeed

1) Clearance is the volume of plasma from which certain substance is removed in a given amount of time. Let’s say that Clearance for urea is 100ml/min (this is just an example not a real urea clearance value!). That means that it takes kidneys 1 min to remove all of the urea that was in 100 ml of plasma.

2) Rate of elimination shows how the amount of the substance in the plasma that we see decreasing with time. Let’s say 100 mg of the drug with T1/2=4hrs is administered (so it’s First Order Kinetics). So first we have 100 mg (amount of the drug), after 4 hrs (T1/2) we have 50 mg left. It means 50 mg was eliminated. To calculate the ratio we take that eliminated 50 mg and we divide it by the initial level (100 mg). 50mg/100mg = 50%. The elimination rate is 50% (constant here!).

For drugs with Zero-Order Elimination Rate:
Let’s say that initial amount in plasma is 100 mg and a constant amount of drug eliminated per unit time (let’s say also 4 hrs) is 10 mg.
We start with 100 mg, after 4hrs we have 90 mg of the drug left in plasma. So we see a decrease by 10 mg. Elimination rate is 10 mg/100 mg = 10%. After another 4 hrs we have 80 mg of the drug left. Again drop by 10 mg but the initial amount here was 90 mg so the elimination rate is 10/90=11,1%. Try to do the calculations after next 4,8 and 12 hours – you’ll see the pattern Here the elimination rate changes with the dose of the drug.
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#9
04-04-2012
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[QUOTE=Casandra;108668]
Quote:
 Originally Posted by Kabutar111 I know its stupid but can you please explain the difffrence b/w clearance and rate of elimination? Also rate of elimination = coc/time Which keep changing with every half life ? Stupid question? Wait till you see some of mines in this forum I have like tonz of them! I’ll try to explain. Please don’t be harsh on me if I don’t succeed 1) Clearance is the volume of plasma from which certain substance is removed in a given amount of time. Let’s say that Clearance for urea is 100ml/min (this is just an example not a real urea clearance value!). That means that it takes kidneys 1 min to remove all of the urea that was in 100 ml of plasma. 2) Rate of elimination shows how the amount of the substance in the plasma that we see decreasing with time. Let’s say 100 mg of the drug with T1/2=4hrs is administered (so it’s First Order Kinetics). So first we have 100 mg (amount of the drug), after 4 hrs (T1/2) we have 50 mg left. It means 50 mg was eliminated. To calculate the ratio we take that eliminated 50 mg and we divide it by the initial level (100 mg). 50mg/100mg = 50%. The elimination rate is 50% (constant here!). For drugs with Zero-Order Elimination Rate: Let’s say that initial amount in plasma is 100 mg and a constant amount of drug eliminated per unit time (let’s say also 4 hrs) is 10 mg. We start with 100 mg, after 4hrs we have 90 mg of the drug left in plasma. So we see a decrease by 10 mg. Elimination rate is 10 mg/100 mg = 10%. After another 4 hrs we have 80 mg of the drug left. Again drop by 10 mg but the initial amount here was 90 mg so the elimination rate is 10/90=11,1%. Try to do the calculations after next 4,8 and 12 hours – you’ll see the pattern Here the elimination rate changes with the dose of the drug.
Thanks for making it clear 🙏

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#10
04-04-2012
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Quote:
 Originally Posted by DocSikorski No its not E its A. Rate is constant, 50% is eliminated. Its First Order kinetics. I feel like Kaplan Biobchem after-chapter questions are poorly written
he is right it is First order elimination
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#11
01-29-2014
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drug clearance is not constant for a drug with a zero oder elimination..what does it mean.. can any 1 explain ??
#12
08-19-2014
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[QUOTE=Casandra;108668]
Quote:
 Originally Posted by Kabutar111 I know its stupid but can you please explain the difffrence b/w clearance and rate of elimination? Also rate of elimination = coc/time Which keep changing with every half life ? Stupid question? Wait till you see some of mines in this forum I have like tonz of them! I’ll try to explain. Please don’t be harsh on me if I don’t succeed 1) Clearance is the volume of plasma from which certain substance is removed in a given amount of time. Let’s say that Clearance for urea is 100ml/min (this is just an example not a real urea clearance value!). That means that it takes kidneys 1 min to remove all of the urea that was in 100 ml of plasma. 2) Rate of elimination shows how the amount of the substance in the plasma that we see decreasing with time. Let’s say 100 mg of the drug with T1/2=4hrs is administered (so it’s First Order Kinetics). So first we have 100 mg (amount of the drug), after 4 hrs (T1/2) we have 50 mg left. It means 50 mg was eliminated. To calculate the ratio we take that eliminated 50 mg and we divide it by the initial level (100 mg). 50mg/100mg = 50%. The elimination rate is 50% (constant here!). For drugs with Zero-Order Elimination Rate: Let’s say that initial amount in plasma is 100 mg and a constant amount of drug eliminated per unit time (let’s say also 4 hrs) is 10 mg. We start with 100 mg, after 4hrs we have 90 mg of the drug left in plasma. So we see a decrease by 10 mg. Elimination rate is 10 mg/100 mg = 10%. After another 4 hrs we have 80 mg of the drug left. Again drop by 10 mg but the initial amount here was 90 mg so the elimination rate is 10/90=11,1%. Try to do the calculations after next 4,8 and 12 hours – you’ll see the pattern Here the elimination rate changes with the dose of the drug.
Thank you for the explanation. This is what I think
I agree with everything except that rate of elimination does not need to be converted into percentage, It's just the amount of the substrate eliminated per unit of time as you said but not the percent. That's why the rate of elimination varies directly with the dose in first-order kinetics and is constant in Zero-order kinetics. So the answer to the test is E. This is the half-life what is constant in first-order kinetics and varies with the zero-order kinetics.
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#13
08-20-2014
 USMLE Forums Addict Steps History: Not yet Posts: 104 Threads: 13 Thanked 32 Times in 24 Posts Reputation: 42

[QUOTE=DrThea;447786]
Quote:
 Originally Posted by Casandra Thank you for the explanation. This is what I think I agree with everything except that rate of elimination does not need to be converted into percentage, It's just the amount of the substrate eliminated per unit of time as you said but not the percent. That's why the rate of elimination varies directly with the dose in first-order kinetics and is constant in Zero-order kinetics. So the answer to the test is E. This is the half-life what is constant in first-order kinetics and varies with the zero-order kinetics.
How would you define clearance then? ROE and clearance can be mixed up, so can you please differentiate between them. This part of pharmacology is heavily tested, so it's best to get the concept right!
#14
08-20-2014
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[QUOTE=eizou;448410]
Quote:
 Originally Posted by DrThea How would you define clearance then? ROE and clearance can be mixed up, so can you please differentiate between them. This part of pharmacology is heavily tested, so it's best to get the concept right!
[QUOTE=Casandra;108668]
Quote:
 Originally Posted by Kabutar111 1) Clearance is the volume of plasma from which certain substance is removed in a given amount of time. Let’s say that Clearance for urea is 100ml/min (this is just an example not a real urea clearance value!). That means that it takes kidneys 1 min to remove all of the urea that was in 100 ml of plasma. 2) Rate of elimination shows how the amount of the substance in the plasma that we see decreasing with time. Let’s say 100 mg of the drug with T1/2=4hrs is administered (so it’s First Order Kinetics). So first we have 100 mg (amount of the drug), after 4 hrs (T1/2) we have 50 mg left. It means 50 mg was eliminated. To calculate the ratio we take that eliminated 50 mg and we divide it by the initial level (100 mg). 50mg/100mg = 50%. The elimination rate is 50% (constant here!).
Clearance is volume of the plasma from which certain substance is removed in a given amount of time as Casandra said. It is 100ml/min from above example, on the other hand Rate of elimination is the amount of substance eliminated per unit of time. According to the Casandra's second example during the first half-life rate of elimination is 50 mg per 4 hrs 50mg/4hrs, during the 2nd half-life - rate of elimination is 25mg/4hrs, 3rd- 12.5mg/4hrs. So the rate of elimination changes with the blood concentration of the drug. There is constant proportion of the drug -50% eliminated per 4 hour but not the constant amount. I would add that time to metabolize 50% of the drug - half-life is constant which is 4hrs.
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#15
08-21-2014
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[QUOTE=DrThea;449074][QUOTE=eizou;448410]

Quote:
 Originally Posted by Casandra Clearance is volume of the plasma from which certain substance is removed in a given amount of time as Casandra said. It is 100ml/min from above example, on the other hand Rate of elimination is the amount of substance eliminated per unit of time. According to the Casandra's second example during the first half-life rate of elimination is 50 mg per 4 hrs 50mg/4hrs, during the 2nd half-life - rate of elimination is 25mg/4hrs, 3rd- 12.5mg/4hrs. So the rate of elimination changes with the blood concentration of the drug. There is constant proportion of the drug -50% eliminated per 4 hour but not the constant amount. I would add that time to metabolize 50% of the drug - half-life is constant which is 4hrs.
Great explanation! Thanks for your time mate.

#16
08-21-2014
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Just another quick question that popped to my head; So the clearance remains constant in FOE? Increasing the dose of the drug will therefore increase the ROE but not the clearance right? Am I getting this right?
#17
08-21-2014
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Quote:
 Originally Posted by eizou Just another quick question that popped to my head; So the clearance remains constant in FOE? Increasing the dose of the drug will therefore increase the ROE but not the clearance right? Am I getting this right?

You are welcome
You are right. Clearance stays the same regardless of the plasma concentration of the drug eliminating with the first-order kinetics. I think because constant proportion is eliminated per unit of time this means that constant volume of blood is cleared per unit of time.

Let's say 100 mg of drug is given, after 4 hours blood concentration is 20 mg/l, because 50 mg was removed that means that 2.5l per 4 hours was cleared (50 mg per 4 hours divided by 20 mg/l). By the same way after next 4 hours 25 mg was removed and so blood concentration should halved also - 10 mg/l, because 25 mg was removed in 4 hours 25/10=2.5l of blood was cleared again.

Also with the zero-order kinetics clearance isn't constant.
#18
08-22-2014
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I honestly don't get the example you used.
#19
04-22-2015
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IN zero order kinetics rate of elimination is constant, which is independent of plasma conc
Where as in first order kinetics, as given in above question rate of elimination is proportional with plasma conc...

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