Bioequivalence and Bioavailability Forum

kishorpatil ☆ 2010-11-22 05:50 (5687 d 23:02 ago) Posting: # 6182 Views: 8,416	Regarding Time point selection of IV infusion formulation [Design Issues] Post reply
	Dear all, can anybody tell me time point selection for one of the intravenous infusion formulation having the Tmax 1 hr and Half life 2 hrs. I hope u will revert back to me. Regard Kishor Patil Edit: Category changed. [Helmut]

Helmut
★★★

Vienna, Austria,
2010-11-22 15:42
(5687 d 13:10 ago)

@ kishorpatil
Posting: # 6185
Views: 7,760

Time points (infusion)

Post reply

Dear Kishor!

❝ […] time point selection for one of the intravenous infusion formulation having the Tmax 1 hr and Half life 2 hrs.

By t_max 1 hr you mean the duration of the infusion, I guess? We must distinguish whether you will analyze your data by means of NCA or PK modeling. If you go with NCA, I would suggest to take two blood samples prior to 1 hr, namely at ≈15 min an ≈45 min. If you want to perform PK modeling, you don’t have to sample prior to the end of infusion at all - the infusion rate is a fixed parameter and must not be covered by data (although one sample may result in more stable fits). It is of paramount importance to record the actual duration (not the planned one).

For the sampling time points in the elimination phase you must consider the following:

Based on the lowest expected C_max in any (!) of the subjects calculate the last time point where you can measure ≥LLOQ. Your elimination rate is k_el = ln(2)/2=0.34657.
The time course of post-infusion concentrations (in % of C_max) is given by C_t = 100·e^-k_el·(t-t_inf), where t_inf is the duration of the infusion. Solving the equation for the common requirement of C_last = 5 % of C_max gives you the last time point of 9.64 hours: t_z=[k_el·t_inf+ln(100/5)]/k_el. If your analytical method is able to measure lower values, fine.
Once you have determined t_z, calculate the post-infusion sampling time points according to this algorithm. Plan for as many time points as your budget allows.

—
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Helmut Schütz

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kishorpatil ☆ 2010-11-23 11:54 (5686 d 16:58 ago) (edited on 2010-11-23 12:10) @ Helmut Posting: # 6194 Views: 7,418	Time points (infusion) Post reply
	Dear sir, I am very thanks for u r suggestion but i did not get what is NCA modeling? I hope u will clarify the same. Regards Kishor Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]

Helmut
★★★

Vienna, Austria,
2010-11-23 14:57
(5686 d 13:55 ago)

@ kishorpatil
Posting: # 6198
Views: 8,234

NCA = model independent

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Dear Kishor!

❝ […] I am very thanks for u r suggestion

Welcome. Please see this post.

❝ […] i did not get what is NCA modeling?

Maybe my phrase ‘… by means of NCA or PK modeling’ was ambigous (‘or’ = the exclusive disjunction ˅). There’s no ‘NCA modeling’. On the contrary NCA (Noncompartmental Analysis) does not assume a particular pharmacokinetic (compartmental) model. The analysis is done by some variant of the trapezoidal rule (AUC, AUMC) and using the observed C_max. For details see one of my lectures. If you calculate the MRT, don’t forget that MRT=AUMC/AUC is only valid for extravascular data; for infusions MRT=AUMC/AUC-t_inf/2 applies.

P.S: Sometimes NCA is called SHAM (Shape, Height, Area, Moments).
Nick Holford usually adds: aka Walt Disney School of PK Methodology. █▓▒░

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Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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kishorpatil
☆

2010-11-26 10:35
(5683 d 18:17 ago)

@ Helmut
Posting: # 6235
Views: 7,531

Details time points

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Dear sir,

As per our discussion Is this correct time point for the Drug having Tmax 1 hr and T half 2 hrs as intravenous infusion.

Details Time Points: 0.00, 0.25, 0.75, 1.00, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0.

I hope u will provide the correct time point to me

Regards
Kishor Patil

Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]

Helmut
★★★

Vienna, Austria,
2010-11-26 13:59
(5683 d 14:53 ago)

@ kishorpatil
Posting: # 6238
Views: 7,484

Ballpark figure(s)

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Dear Kishor!

❝ Is this correct time point for the Drug having Tmax 1 hr and T half 2 hrs as intravenous infusion.

❝ […] 0.00, 0.25, 0.75, 1.00, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0.

IMHO, no. You may use them (as any others), but they are not optimal.

❝ I hope u will provide the correct time point to me

Sorry, that's not the way it works here. If you tell me how you got your numbers (especially the 8 hrs), we can continue the discussion. If I simply tell you my sampling scheme, will you ask me again for all further studies?

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Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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kishorpatil ☆ 2010-11-29 12:41 (5680 d 16:11 ago) @ Helmut Posting: # 6242 Views: 7,456	Ballpark figure(s) Post reply
	Nor dear its ok for me. I thing the time point I design its correct. Regards Kishor Edit: Full quote removed - like in *all* your previous replies! Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut]

Helmut ★★★ Vienna, Austria, 2010-11-29 14:44 (5680 d 14:08 ago) @ kishorpatil Posting: # 6244 Views: 7,364	Believes... Post reply
	❝ I thing the time point I design its correct. Believe those who are seeking the truth. Doubt those who find it. André Gide — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes

kishorpatil ☆ 2010-11-30 06:56 (5679 d 21:56 ago) (edited on 2010-11-30 09:09) @ Helmut Posting: # 6247 Views: 7,321	Believes... Post reply
	Dear helmut, Please tell me shall i proceed with above menti0ned time point or not. I will wait for u r reply. Regards Kishor Edit: Full quote removed, like in all your previous responses. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]

Helmut
★★★

Vienna, Austria,
2010-11-30 16:38
(5679 d 12:14 ago)

@ kishorpatil
Posting: # 6256
Views: 7,504

Are you serious?

Post reply

Dear Kishor!

❝ Please tell me shall i proceed with above menti0ned time point or not.

❝ I will wait for u r reply.

In this post I mentioned some points important for the design and cross-referenced to an algorithm.
Here you came up with a rule of thumb sampling schedule, obviously ignoring (or not comprehending) my suggestions. You were asking whether this schedule is ‘correct’.
My answer was no. I was asking how you derived your schedule.
You called me ‘dear’ (how sweet!), telling me that you think your schedule is right.
Obviously you are waiting for some kind of ‘approval’ from my side. No way! Do whatever you like – I still think that your design is suboptimal. The difference between my design and yours is, that mine is based on bioanalytics/PK and yours – on what?
We (Ohlbe and myself) had to edit all (!) of your posts getting rid of f…g full quotes.
I reminded you there not to use this awful SMS-style of posting.

To make a long story short:Comply with the Forum’s Policy – otherwise I will block your account.

I will not discuss your design any longer unless you give an explanation how you derived it.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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kishorpatil
☆

2010-12-09 06:10
(5670 d 22:42 ago)

@ Helmut
Posting: # 6277
Views: 7,157

Are you serious?

Post reply

Dear sir,

its not like that.I was derived it from tmax and Thalf of drug according submission of study.As its IV infusion and its tmax 1 hrs so that The sampling schedule should include frequent sampling around predicted tmax to provide a reliable estimate of peak exposure and I want to to avoid
Cmax being the first point of a concentration time curve as our submission to Europe so according to that i determined the Schedued ok.

Regards
Kishor Patil

Edit: Full quote removed. Unbelievable. You’re a troll. :angry:

[Helmut]

NewInPK
☆

2011-01-31 06:47
(5617 d 22:05 ago)

@ Helmut
Posting: # 6517
Views: 6,878

NCA = model independent

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❝ If you calculate the MRT, don't forget that MRT=AUMC/AUC is only valid for extravascular data;

Dear HS,

I was searching for more information about the meaning of AUMC and have found this post. On this website (http://www.uiowa.edu/~c046138/tut-noncomp.htm) it is explained that MRT = AUMC/AUC only for instantaneous administration. I am not sure if that means "all at once" including IV and oral, as opposed to infusion and slow release, or if it means only IV bolus. If the latter is true, I wonder why is MRT calculated in WinNonlin with model 200 = extravascular?

As far as AUMC is concerned, besides the "area under the first moment curve," which doesn't help me much, the only explanation I have found so far is "a measure of the extent of distribution." Assuming I will be able to understand what it means, would it be useful to compare this parameter when comparing two different groups (for instance, different age groups)?

Thanks a lot!

Regarding Time point selection of IV infusion formulation [Design Issues]

Time points (infusion)

Time points (infusion)

NCA = model independent

Details time points

Ballpark figure(s)

Ballpark figure(s)

Believes...

Believes...

Are you serious?

Are you serious?

NCA = model independent