Imph ★ 20220925 15:52 (626 d 18:40 ago) Posting: # 23318 Views: 3,772 

hello, I want to use a pharmacokinetic data from the literature and this data is provided in the form: mean ±SD, is it correct to use only the mean without taking into account the standard deviation? For example I want to calculate a washout duration of seven times t1/2. This t1/2 is provided in the form: mean ±SD. Is it right to do "7 x t1/2 mean" without taking into consideration the SD?. Thank you in advance Edit: Category and subject line changed; see also this post #1. [Helmut] 
Helmut ★★★ Vienna, Austria, 20220925 18:08 (626 d 16:23 ago) @ Imph Posting: # 23319 Views: 3,137 

Hi Imph, ❝ Is it right to do "7 x t1/2 mean" without taking into consideration the SD? That’s extremely risky. You may see residual concentrations in subjects with a half life longer than the reported mean and have to exclude them to avoid carryover (i.e., if the predose concentration is >5% C_{max}). See this presentation (slides 64/65). — Diftor heh smusma 🖖🏼 Довге життя Україна! _{} Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes 
Imph ★ 20220926 17:24 (625 d 17:07 ago) @ Helmut Posting: # 23320 Views: 3,072 

Hi, Thank you very much for your valuable informations. I would like to know if this method can be applied to each pharmacokinetic measurement, for example to determine the duration of the sampling (5 x t1/2) or to calculate the predose limit of 5% Cmax when the Cmax is provided in the literature under mean+/SD. Why plan for 95% coverage (z0.95 = 1.96), is it related to alpha =5%. In the reference you gave, a normal distribution is assumed, but pharmacokinetic measurements do not generally follow a normal distribution but a lognormal one. Does this method still apply? Thank you verry much. 
Shuanghe ★★ Spain, 20220926 19:34 (625 d 14:57 ago) @ Imph Posting: # 23321 Views: 3,031 

Hi Imph ❝ I would like to know if this method can be applied to each pharmacokinetic measurement, for example to determine the duration of the sampling (5 x t1/2) or to calculate the predose limit of 5% Cmax when the Cmax is provided in the literature under mean+/SD. I don't know about "every" PK parameter, but FDA use this approach to plan partial AUC as well. For example, for methylphenidate HCl ER tablet, among other parameters, FDA requests partial AUC_{03h} and AUC_{04h} for fasting and fed studies, respectively. The reason was that the Tmax was 2h under fasting and 3h under fed. the standard deviation (SD) of Tmax is about 0.5h, so 2 x SD is 1h, according to FDA: > "For Tmax, two standard deviations = 1.0; Generally, approximately 95% of observations fall within two standard deviations of the mean; Thus, since the Tmax from the immediaterelease portion of this formulation is about 2 hours under fasting conditions and 3 hours under fed conditions, pAUCs calculated to 03 hours in a fasting BE study and 04 hours in a fed BE study should capture the responses of 95% of the subjects. This should provide assurance that a test and reference product will be therapeutically equivalent over the early part of the daily dosing interval, corresponding to onset of response." (see ref linked here) This is the same as what Helmut did for t_{1/2} in his PPT cited in previous post. ❝ In the reference you gave, a normal distribution is assumed, but pharmacokinetic measurements do not generally follow a normal distribution but a lognormal one. Does this method still apply? Well, Tmax is discrete so it is not normal distribution either. FDA still use it for the approximation for pAUC. I'd use this 5 x (mean(PK) + 2xSD(PK)) instead of the empirical "7 x mean(PK)". — All the best, Shuanghe 
Helmut ★★★ Vienna, Austria, 20220926 19:35 (625 d 14:56 ago) @ Imph Posting: # 23322 Views: 3,061 

Hi Imph, ❝ I would like to know if this method can be applied to each pharmacokinetic measurement, for example to determine the duration of the sampling (5 x t1/2) or to calculate the predose limit of 5% Cmax when the Cmax is provided in the literature under mean+/SD. In principle, yes. I prefer to start with a single dose profile (even if read from a published figure) and perform nonparametric superposition. ❝ Why plan for 95% coverage (z0.95 = 1.96), is it related to alpha =5%. Convention. You can use a more conservative value. ❝ In the reference you gave, a normal distribution is assumed, but pharmacokinetic measurements do not generally follow a normal distribution but a lognormal one. Does this method still apply? You are right. But if the arithmetic mean ± SD is all you have… If you have results for the geometric mean, better, of course. — Diftor heh smusma 🖖🏼 Довге життя Україна! _{} Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes 
Helmut ★★★ Vienna, Austria, 20220927 13:52 (624 d 20:40 ago) @ Imph Posting: # 23323 Views: 3,005 

Hi Imph, if you have individual half lives, you can calculate the geometric mean / SD and use any confidence interval you like. For planning the washout use the upper confidence limit. script (results in blue):
— Diftor heh smusma 🖖🏼 Довге життя Україна! _{} Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes 
Imph ★ 20221025 11:21 (596 d 23:10 ago) @ Helmut Posting: # 23348 Views: 2,808 

Hello, Thank you very much it was a great help for us. Best regards. 
Imph ★ 20230527 01:31 (383 d 09:00 ago) @ Helmut Posting: # 23571 Views: 1,675 

❝ ❝ Is it right to do "7 x t1/2 mean" without taking into consideration the SD? ❝ ❝ See this presentation (slides 64/65). Hi, I am here again about the way of taking into account the standard deviation described on page 64 of the presentation. Using the t1/2 +/SD given in the SmPC, what sample size can be used? is it correct to use the sample size I plan to use in my study? Thank you very much. 
Helmut ★★★ Vienna, Austria, 20230527 08:52 (383 d 01:39 ago) @ Imph Posting: # 23572 Views: 1,639 

Hi Imph, ❝ […] Using the t1/2 +/SD given in the SmPC, what sample size can be used? is it correct to use the sample size I plan to use in my study? Yes. — Diftor heh smusma 🖖🏼 Довге життя Україна! _{} Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes 
Imph ★ 20230527 10:36 (382 d 23:56 ago) @ Helmut Posting: # 23574 Views: 1,603 

Thank you very much. 