Pharmacokinetics problem: Is this problem impossible?

[Chuck61686]

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A pharmacokinetics homework problem I have.

All the information given...
Dose: 100 mg
Infusion time: 1-hour
Volume of distribution: 15 liters
Dosing interval: 12 hours

Question: What will be the peak steady state concentration? And what will be the trough steady state concentration?

For the life of me I can't figure this out! With the limited info provided I can't solve for the elimination rate constant/half life/clearance, which is needed. Anyone agree with me that this is not solvable? I'm not asking for the answer, I just want to know if this is can even be solved without more information. Thanks!

 

[njac]

I would think that you have the information for peak, but not for trough.

 

[KARM12]

For a bolus dose?

dose = Vd x concentration

Edit...sorry didn't see steady state in your question. Do they say the drug is gentamicin? If so you could estimate using population kinetics.

 

[Its Z]

You have enough information for extrapolated peak after the first dose..which is 6.67ug/ml. Because elimination constance (Ke) and/or t1/2 were not given, it's not possible for me to calculate the trough and steady state levels.

 

[Chuck61686]

For a bolus dose?

dose = Vd x concentration

Edit...sorry didn't see steady state in your question. Do they say the drug is gentamicin? If so you could estimate using population kinetics.

Nope, no information on what the drug is. All the data I listed is what I was given in the question. 🙁

 

[Chuck61686]

You have enough information for extrapolated peak after the first dose..which is 6.67ug/ml. Because elimination constance (Ke) and/or t1/2 were not given, it's not possible for me to calculate the trough and steady state levels.

That's what I'm saying...key word: steady state. Glad to see a pharmacist agree with me.

 

[Its Z]

That's what I'm saying...key word: steady state. Glad to see a pharmacist agree with me.

But I'm not a very good pharmist.

 

[npage148]

Id also argue that you could not figure out the peak after the first dose. If the T1/2 is very short there could be significant elimination before the infusion is done making the peak lower than Dose/Vd. so you can't get anything with the info.

 

[powertoold]

A pharmacokinetics homework problem I have.

All the information given...
Dose: 100 mg
Infusion time: 1-hour
Volume of distribution: 15 liters
Dosing interval: 12 hours

Question: What will be the peak steady state concentration? And what will be the trough steady state concentration?

For the life of me I can't figure this out! With the limited info provided I can't solve for the elimination rate constant/half life/clearance, which is needed. Anyone agree with me that this is not solvable? I'm not asking for the answer, I just want to know if this is can even be solved without more information. Thanks!

So you don't know what drug it is? It's probably not a vanco dose (since it's low). If anything, it can be gent / tobra at a 1.5mg/kg traditional dose. Usually, gent / tobra dosing intervals are 2-3 half-lives.

If you know what drug it is, then you can guestimate the half-life. After that, you can figure out everything.

With the current information, you can't figure out the peak (unless the half-life is > 6 hours, in that case, you can use a repetitive bolus model instead of a repetitive infusion model) or trough concentration.

 

[Its Z]

So you don't know what drug it is? It's probably not a vanco dose (since it's low). If anything, it can be gent / tobra at a 1.5mg/kg traditional dose. Usually, gent / tobra dosing intervals are 2-3 half-lives.

If you know what drug it is, then you can guestimate the half-life. After that, you can figure out everything.

With the current information, you can't figure out the peak (unless the half-life is > 6 hours, in that case, you can use a repetitive bolus model instead of a repetitive infusion model) or trough concentration.

No it's not. Aminoglycoside is now typically dosed in extended interval. Like 24, 36, and 48 hours.

 

[powertoold]

No it's not. Aminoglycoside is now typically dosed in extended interval. Like 24, 36, and 48 hours.

No it's not. I'm talking about traditional aminoglycoside dosing (i.e. usually in traditional aminoglycoside dosing, the intervals are 2-3 half-lives). You're talking about once daily. Many physicians still use traditional dosing because they're not accustomed to once daily, which is easier to dose and has similar efficacy to traditional dosing.

Also, traditional dosing is used when a PT has an exclusion criteria for once daily, such as hemodialysis, burns, pregnancy, enterococcal endocarditis, and others I can't remember.

 

[Its Z]

No it's not. I'm talking about traditional aminoglycoside dosing (i.e. usually in traditional aminoglycoside dosing, the intervals are 2-3 half-lives). You're talking about once daily. Many physicians still use traditional dosing because they're not accustomed to once daily, which is easier to dose and has similar efficacy to traditional dosing.

Wrong.

Also, traditional dosing is used when a PT has an exclusion criteria for once daily, such as hemodialysis, burns, pregnancy, enterococcal endocarditis, and others I can't remember.

You left out peritoneal dialysis, peds, myasthenia gravis and some more.

More aminoglycosides are now dosed in extended interval with either 5 to 7mg/kg then traditional dosing which is more toxic yet less clinically effective.
Just because your little hospital does it one way doesn't indicate what's going on in the industry. Your phyisican's aren't used to extended dosing? Good Lord...it's been out for 15+ years? Your clinical department must suck.

 

[Quiksilver]

A pharmacokinetics homework problem I have.

All the information given...
Dose: 100 mg
Infusion time: 1-hour
Volume of distribution: 15 liters
Dosing interval: 12 hours

Question: What will be the peak steady state concentration? And what will be the trough steady state concentration?

For the life of me I can't figure this out! With the limited info provided I can't solve for the elimination rate constant/half life/clearance, which is needed. Anyone agree with me that this is not solvable? I'm not asking for the answer, I just want to know if this is can even be solved without more information. Thanks!

This problem is not impossible. You use the method of superposition. You need to figure out an accumulation ratio, r.
Tau is the dosing interval
r = 1/(1-e^-k*tau)
Css, p =Dose/Vd *r
Css,t = Css,p * e^-k*tau
Average Css = F*Dose/CL * Tau
Double check this, its been awhile since I have done this ****.
Hope this helps.

 

[Praziquantel86]

This problem is not impossible. You use the method of superposition. You need to figure out an accumulation ratio, r.
Tau is the dosing interval
r = 1/(1-e^-k*tau)
Css, p =Dose/Vd *r
Css,t = Css,p * e^-k*tau
Average Css = F*Dose/CL * Tau
Double check this, its been awhile since I have done this ****.
Hope this helps.

No elimination rate constant, can't do it.

 

[powertoold]

Wrong.



You left out peritoneal dialysis, peds, myasthenia gravis and some more.

More aminoglycosides are now dosed in extended interval with either 5 to 7mg/kg then traditional dosing which is more toxic yet less clinically effective.
Just because your little hospital does it one way doesn't indicate what's going on in the industry. Your phyisican's aren't used to extended dosing? Good Lord...it's been out for 15+ years? Your clinical department must suck.

Yes, I know. In my initial post, I thought I made it clear I was talking about traditional aminoglycoside dosing, which is what many of the aminoglycoside PK dosing questions are based on... You can't really make good PK questions based on once daily dosing because all you'd need to do is 5mg/kg then have a random level 6-14 hours later, look on the nomogram, and determine the interval.

I'm not sure why you're attacking my knowledge, but in this case, I'm presenting the correct logic and facts. Also, another piece of info that points towards a traditional aminoglycoside dosing problem is the 15L volume of distribution, which is around 0.25L/kg (population average for aminoglycosides) for a 60-70kg person.

I'm not disagreeing with you about traditional vs once daily dosing. You may be right that traditional is more toxic and less efficacious (although I doubt there's a concensus on this). The initial debate is about whether the original problem is about traditional aminoglycoside dosing, and I believe I presented good evidence to support this fact.

 

[Quiksilver]

No elimination rate constant, can't do it.

Ah damn. I fail for not reading carefully. I mean the only thing I can think of is that you have to make an assumption based on the dosing interval. Are you to assume that the interval is the half-life. I know that its a completely incorrect assumption but its all I can think of.

Yes, I know. In my initial post, I thought I made it clear I was talking about traditional aminoglycoside dosing, which is what many of the aminoglycoside PK dosing questions are based on... You can't really make good PK questions based on once daily dosing because all you'd need to do is 5mg/kg then have a random level 6-14 hours later, look on the nomogram, and determine the interval.

I'm not sure why you're attacking my knowledge, but in this case, I'm presenting the correct logic and facts. Also, another piece of info that points towards a traditional aminoglycoside dosing problem is the 15L volume of distribution, which is around 0.25L/kg (population average for aminoglycosides) for a 60-70kg person.

I'm not disagreeing with you about traditional vs once daily dosing. You may be right that traditional is more toxic and less efficacious (although I doubt there's a concensus on this). The initial debate is about whether the original problem is about traditional aminoglycoside dosing, and I believe I presented good evidence to support this fact.

Dude the drug is irrelevant to the problem. In a basic PK type of problem this can be a dangerous thing to do. Its almost like you want to cheat your way through the problem.

PS Most places use Extended Interval Dosing with aminoglycosides. If you have a pharmacy dept that knows anything about PK they would be pushing this issue. if you are or are not aware its high troughs that correspond to toxicity, not high peaks.

 

[powertoold]

Dude the drug is irrelevant to the problem. In a basic PK type of problem this can be a dangerous thing to do. Its almost like you want to cheat your way through the problem.

PS Most places use Extended Interval Dosing with aminoglycosides. If you have a pharmacy dept that knows anything about PK they would be pushing this issue. if you are or are not aware its high troughs that correspond to toxicity, not high peaks.

The drug is definitely relevant for the problem.

I don't understand your point about something being dangerous?

I have no interest in cheating my way through the problem. I'm just presenting information that may be relevant to the type of problem it may be. All the information presented seems to point towards a traditional aminoglycoside dosing problem. The fact that ODA is widely used isn't relevant to the problem.

I find it funny that Z would find a way to put down my institution simply based on the fact that I said traditional aminoglycoside dosing is usually given at 2-3 half lives. I don't know what's the big deal about ODA, but it obviously has little to do with this problem since the doses and intervals for ODA are much different.

To summarize, here are the reasons I think this is a traditional / conventional gent / tobra dosing question:

• 100mg is around 1-2mg/kg, which is the dose of gent / tobra
• Intervals are typically 2-3 half lives (usually around 6 hours), so 12 hours makes sense
• A Vd of 15L corresponds to the pop. avg of 0.25L/kg for 60-70kg person
• Many PK problems are based on conventional / traditional aminoglycoside dosing

If I had to provide an answer, I'd assume the half-life was around 4-6 hours and find the rate constant from there. With the rate constant, I can figure out everything else.

 

[Its Z]

I find it funny that Z would find a way to put down my institution simply based on the fact that I said traditional aminoglycoside dosing is usually given at 2-3 half lives. I don't know what's the big deal about ODA, but it obviously has little to do with this problem since the doses and intervals for ODA are much different.

I put down your institution because you said your docs are uncomfortable with ODA which indicates your pharmacy department is sitting on their arses.

To summarize, here are the reasons I think this is a traditional / conventional gent / tobra dosing question:

• 100mg is around 1-2mg/kg, which is the dose of gent / tobra
• Intervals are typically 2-3 half lives (usually around 6 hours), so 12 hours makes sense
• A Vd of 15L corresponds to the pop. avg of 0.25L/kg for 60-70kg person
• Many PK problems are based on conventional / traditional aminoglycoside dosing

If I had to provide an answer, I'd assume the half-life was around 4-6 hours and find the rate constant from there. With the rate constant, I can figure out everything else.

Typical 1/2 life of AG is 2 to 3 hours.

 

[Its Z]

I understand why you'd think the OP's drug is an AG like gent or tobra. It's easy to assume that the drug is an AG with the traditional dosing regimen. And I understand the traditional dosing is still taught in school and it should be.

But we have now learned that the extended interval AG is the safe and more efficacious methodology because it prevents sustained high trough which can result in renal toxicity and at the same time the peak of MIC X 10 attained with ODA is more bacteriocidal than the typical peak of 6 to 8 mcg/ml.

I attacked you because you stated matter of factly that AG is dosed 2 to 3 times the t1/2 at a lower mg/kg which is not typically practiced today. The exclusion criteria exists because of the lack of stuides and liability issues more so than than the lack of effectiveness.

It is a vague question. Vague enough to not assume what kind of drug it is. At the same time, the lack of elimination information should tell us that it's not a complete question.

The OP's drug could also be fosphenytoin albeit 15L of Vd is on a higher side yet it would pose an interesting PK phenomenon to workout the michelis menten equation.

 

[Its Z]

The drug is definitely relevant for the problem.

Wrong.

The drug is irelevant. Pharmacokinetic properties of the drug in the patient is what's relavant. For all you know, it could be vanco for a 20kg pedi with renal insufficiency being used to treat MRSA UTI.

Population data should not be applied to assume anything in this case as the Ke and/or t1/2 is the critical component of the equation yet unknown.

Incomplete question.

 

[powertoold]

I put down your institution because you said your docs are uncomfortable with ODA which indicates your pharmacy department is sitting on their arses.

I just said many docs are still uncomfortable. Perhaps your definition of "many" is different than mine. Not sure how you can conclude my pharmacy dept sucks from this.

Typical 1/2 life of AG is 2 to 3 hours.

True, for CrCl > 60mL/min. My 6 hour estimate is too high. I should have said 4-6 hours.

The drug is irelevant.

I still disagree with this. In PK classes, the concept of population vs. patient specific parameters is emphasized again and again. With the information presented, we are to assume that the patient specific parameters are not yet available, so we'd need to know the drug in order to determine which population PK values to use.

I'm not sure about your PK class, but in mine, I had to memorize the population PK values for vanco and the aminoglycosides.

 

[Its Z]

I'm not sure about your PK class, but in mine, I had to memorize the population PK values for vanco and the aminoglycosides.

As all pharmacy student should. Yet since you don't know what the drug is, you still can't assume a certain Vd belongs to AG or Vanc using the population PK values.

 

[powertoold]

As all pharmacy student should. Yet since you don't know what the drug is, you still can't assume a certain Vd belongs to AG or Vanc using the population PK values.

Bleh, yes, in real pharmacy practice, you wouldn't just assume these things.

Let's put this thing to rest 🙂