maulik963
☆    

India,
2016-04-13 08:06
(1576 d 13:13 ago)

Posting: # 16194
Views: 4,162
 

 Which Tmax to be consider in case of b.i.d. dosing? [NCA / SHAM]

Dear All,

I want to conduct 2-way crossover study with Extended Release (Once daily dosing regimen) Test product and Immediate Release (Two times a day dosing regimen) Reference Product.

Study design is 2-Treatment, 2-period, 2-sequence, single dose of Test product vs. multiple dose of Reference product at 12.0 hours interval.

Considering above details, I need answer/clarification on the below point.

As Reference product is to be given two times a day at 12.00 hours interval, there will be total two Cmax (means two Tmax where maximum concentration achieved).

So which Tmax should be consider? (i.e. The Tmax reported after first dosing or Tmax which is actually a highest value among the two Tmax).

Please note that the molecule does not have the property of giving two distinct peak after single dosing.

Thanks in advance.


Edit: Category changed. [Helmut]
BE-proff
★★  

Russia,
2016-04-13 09:27
(1576 d 11:52 ago)

@ maulik963
Posting: # 16195
Views: 3,445
 

 Which Tmax to be consider in case of b.i.d. dosing?

Hi maulik963,

Why did you decide to take 12h interval, not 13h and 11h?
maulik963
☆    

India,
2016-04-13 13:09
(1576 d 08:11 ago)

@ BE-proff
Posting: # 16197
Views: 3,438
 

 Which Tmax to be consider in case of b.i.d. dosing?

» Why did you decide to take 12h interval, not 13h and 11h?

Reply: The dosage regimen for Immediate release formulation is twice daily thats why second dosing done at 12.0 hours interval.
Helmut
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Vienna, Austria,
2016-04-13 13:49
(1576 d 07:30 ago)

@ maulik963
Posting: # 16199
Views: 3,602
 

 Which Tmax to be consider in case of b.i.d. dosing?

Hi Maulik,

» » Why did you decide to take 12h interval, not 13h and 11h?
»
» Reply: The dosage regimen for Immediate release formulation is twice daily thats why second dosing done at 12.0 hours interval.

That’s not a justification!

» » » As Reference product is to be given two times a day at 12.00 hours interval …

BID does not necessarily mean τ 12 h. What does the label/SmPC of the IR product state? For a lot of “uncomplicated drugs” BID may as well allow for a “convenient” dose regimen (e.g., 7 a.m. and 10 p.m. = τ 15/9 h). For some drugs (antibiotics, anticonvulsants, …) a strictly equal dosing regimen is mandatory. Yet others (diurnal variation in PK) may mandate a fixed dose regimen with unequal intervals in order to minimize fluctuations. Hence, BE-proff’s question makes sense indeed.

Essentially it boils down to the target you had in mind developing the MR formulation. I would explore all PK-metrics in both intervals (pAUC0–τ, Cmax,0–τ, tmax,0–τ and pAUCτ–t, Cmax,τ–t, tmax,τ–t) as well as the global ones (AUC0–t, Cmax, tmax).

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maulik963
☆    

India,
2016-04-16 12:32
(1573 d 08:47 ago)

@ Helmut
Posting: # 16209
Views: 3,256
 

 Which Tmax to be consider in case of b.i.d. dosing?

Dear Helmut,

» Essentially it boils down to the target you had in mind developing the MR formulation. I would explore all PK-metrics in both intervals (pAUC0–τ, Cmax,0–τ, tmax,0–τ and pAUCτ–t, Cmax,τ–t, tmax,τ–t) as well as the global ones (AUC0–t, Cmax, tmax).

Thanks for your valuable information. I understood that all PK-metrics of both dosing interval should be provided but if i wish to conclude the result, Which Cmax i should consider?
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