d_labes
★★★

Berlin, Germany,
2015-10-08 21:57
(3482 d 21:11 ago)

Posting: # 15533
Views: 16,045
 

 Ct curves from single dose to pre­dict multiple dose [Software]

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Dear all,

I have some concentration time curves after single dose application.

Now I have the task to predict from these curves the concentration time course after multiple dosing, assuming lineare kinetics.

Does anybody knows any software to accomplish this task or has some code in f.i. R for superposition the concentration time curves after single dose application?

Best would be without some compartment model fit (NCA).
Second best with using some compartment model.

Any help would be greatly appreciated.
—
Regards,

Detlew
 
Helmut
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Vienna, Austria,
2015-10-08 23:02
(3482 d 20:06 ago)

@ d_labes
Posting: # 15534
Views: 14,457
 

 Phoenix/WinNonlin: Non­Para­metric Super­position

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Dear Detlew,

in Phoenix/WinNonlin there is a dedicated tool called “NonParametric Superpostion” which does exactly what you need.
  • Performs NCA (Pharsight recommends the log trapezoidal); needs a reliable estimate of λz.
  • ⇒ Define doses and dosing intervals.
  • ⇒ Click the button.
    Stacks according to Mr Dost’s “Gesetz der korrespondieren Flächen” (1953). :-D
In R (I don’t have any code):
  • Easy, if you have both equal doses and dosing intervals.
  • Moderate, for unequal doses but equal τs.
  • Nasty, if both can vary. Never seen that in the world of BE anyway.
IIRC there is a similar tool in Kinetica.
PK-Xpress has such a function as well. In a WebEx-presentation last summer it turned out that only the linear trapezoidal was implemented. Not a good idea to stack in each dosing interval another positive bias on top of the ones before.
—
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yjlee168
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Kaohsiung, Taiwan,
2015-10-09 08:39
(3482 d 10:29 ago)

@ d_labes
Posting: # 15535
Views: 14,115
 

 Ct curves from single dose to pre­dict multiple dose

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Dear Detlew,

I assume that you want do following:
  1. to obtain PK parameters first from your single-dose Ct;
    [image]
  2. to use known PK parameters to simulate multiple-dose in general simulations or Monte-Carlo simulations.
    [image]
    (with <= +/-10% uniform errors added to calc. Ct)

    [image]
    (20's MC simulations)

As Helmut said that there are some commercial or freeware software should do the same jobs. Freeware includes Boomer or ADAPT (required FORTRAN compiler).

❝ Does anybody knows any software to accomplish this task or has some code in f.i. R for superposition the concentration time curves after single dose application?


Introducing PKfit if you prefer using R. The plots are created with PKfit. I am very happy to help if you are really interested in using PKfit. Hope this can help.
—
All the best,
-- Yung-jin Lee
bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee
Kaohsiung, Taiwan https://www.pkpd168.com/bear
Download link (updated) -> here
 
d_labes
★★★

Berlin, Germany,
2015-10-09 10:46
(3482 d 08:22 ago)

@ yjlee168
Posting: # 15539
Views: 13,886
 

 Software for superposition

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Dear Yung-jin, dear Helmut,

many thanks for your tips.

@Yung-jin: I will take a closer look at PKfit if time allows. Unfortunately I have very tight time lines (till this evening!:-().

@Helmut: Kinetica? I beg you pardon ... :-D
PK-Xpress seems (beside the spare information given) an "Eierlegende-Wollmilch-Sau". Anybody out there with experiences with that piece of software? Expense?
—
Regards,

Detlew
 
Helmut
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Vienna, Austria,
2015-10-09 16:23
(3482 d 02:45 ago)

@ d_labes
Posting: # 15544
Views: 14,157
 

 PK-Xpress: impressions

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Dear Detlew,

❝ Kinetica? I beg you pardon ... :-D


As long as you don’t want to perform the BE-stats it is OK (& if you can stand the strange user-inter­face). Competitive price.

❝ PK-Xpress seems (beside the spare information given) an "Eierlegende-Wollmilch-Sau".


Leo.

❝ Anybody out there with experiences with that piece of software?


No hands-on experience but last July I endured a two-hours WebEx presentation with the folk in Pune. Observations:
  • Open port 80 (HTTP) during installation – pointing to IP 180.87.43.162; “enable the download of execut­able (.exe) file from web”. That’s a no-go for me.
  • Eventually (!) there is a stand-alone installer. They were unsure about it…
  • Requires Office 2007+ (Excel’s Solver Add-On). Didn’t manage to find out why. Back luck for people using OpenOffice, LibreOffice, or Office 2000 like myself. IMHO Solver is an undocu­mented piece of shit.
  • Automatic algo for λz (based on max R²adj) may include tmax (like in WinNonlin <v6). However, manual selection of time range possible.
  • Only linear trapezoidal method implemented.
  • Extrapolation by Clast/λz. Not possible to use Ĉlast/λz.
  • No partial AUCs.
  • BE-stats. Not for a SASian like you, but might be interesting to others:
    • 2×2×2 cross-overs and two-group parallel. Full stop. No higher order crossovers, no replicate designs.
    • In crossovers subjects as a random effect (FDA). They were unaware of EMA’s all-fixed effects require­­ment.
    • Given the above, no reference-scaling; working on replicate designs. They were sur­prised to hear [sic] that the FDA and EMA require different models.
At the bottom of the webpage you will find

[image] Validation Kit

Don’t know what that means. I’ve sent them our reference datasets…

On 31 July I received an e-mail:

As a part of data refining process, we are working on refining of BE program. As soon as this pro­cess is done we will work on the data provided by you and share the desired outputs.

Haven’t heart anything ever since.

❝ Expense?


They didn’t want to talk about it. Luv told me:

3,000 USD for each of DissoXpress, IvivcXpress, PK-Xpress. If you are going for whole package the cost would be even lesser. Yearly support charges: 20% of license cost per client.

Much cheaper than Phoenix and slightly below Kinetica.

Overall I would say it is an interesting product – which calls for further improvements. For NCA, not that bad. For BE-stats, no way.
—
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d_labes
★★★

Berlin, Germany,
2015-10-09 22:23
(3481 d 20:44 ago)

@ Helmut
Posting: # 15545
Views: 13,735
 

 PK-Xpress: impressions

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Dear Helmut,

THX for your impressions. Does help a lot.

❝ ... Observations:

❝ ● Open port 80 (HTTP) during installation – pointing to IP 180.87.43.162; “enable the download of execut­able (.exe) file from web”. That’s a no-go for me.


For me too. Even at home and not at work. NSA is sending it's regards :angry:.

❝ ● Eventually (!) there is a stand-alone installer. They were unsure about it…


Funny :cool:.

❝ ● Requires Office 2007+ (Excel’s Solver Add-On). Didn’t manage to find out why. Back luck for people using OpenOffice, LibreOffice, or Office 2000 like myself. IMHO Solver is an undocu­mented piece of shit.


Really bizarre.

❝ ● Automatic algo for λz (based on max R²adj) may include tmax (like in WinNonlin <v6). However, manual selection of time range possible.


The last sentence allows myself to be consoled/comforted.

❝ ● Only linear trapezoidal method implemented.

❝ ● Extrapolation by Clast/λz. Not possible to use Ĉlast/λz.

❝ ● No partial AUCs.


Serious shortcomings.

❝ ...

❝ ● Given the above, no reference-scaling; working on replicate designs. They were sur­prised to hear [sic] that the FDA and EMA require different models.


I know! Europe is some miles away from "Hohes A" and "Ohrschinken". And EMA? Who is that? :-D

❝ At the bottom of the webpage you will find

[image] Validation Kit

Don’t know what that means.


Don't use that word val... if I'm beneath you :angry:. Just struggling with that ..., whatever it means!

❝ I’ve sent them our reference datasets… On 31 July I received an e-mail:

As a part of data refining process, we are working on refining of BE program. As soon as this pro­cess is done we will work on the data provided by you and share the desired outputs.

Haven’t heart anything ever since.


Sooner or later they have to take into account the Holy Grail :-D of val... Oh no! Again that word!

❝ ❝ Expense?

❝ ... Luv told me: 3,000 USD for each of DissoXpress, IvivcXpress, PK-Xpress. If you are going for whole package the cost would be even lesser. Yearly support charges: 20% of license cost per client. Much cheaper than Phoenix and slightly below Kinetica.


Compared with SAS this is a "Schnäppchen".

❝ Overall I would say it is an interesting product – which calls for further improvements. For NCA, not that bad.


Empasis by me. Lets watch it evolving.

❝ For BE-stats, no way.


As you know I'm doing all the stats in SAS. Therefore this is not so important for me.

BTW:
It's a nightmare to answer to some posters which have mastered the [list][/list] construct in between the list points, especially if the list is also hierarchical. And some posters are using this to the excess ;-). Is there a way to simplify matters? I struggle since hours with an answer post to Yours.

Another wish: If I adapt the edit area to greater dimensions and press than PREVIEW it shrinkens to it's standard size. Is it possible to change this behavior?
—
Regards,

Detlew
 
Helmut
★★★
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Homepage
Vienna, Austria,
2015-10-10 03:06
(3481 d 16:01 ago)

@ d_labes
Posting: # 15546
Views: 14,439
 

 OT: list limbo and (X)HTML

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Dear Detlew,

❝ ❝ ... Luv told me: 3,000 USD for each of DissoXpress, IvivcXpress, PK-Xpress. If you are going for whole package the cost would be even lesser. Yearly support charges: 20% of license cost per client. Much cheaper than Phoenix and slightly below Kinetica.

❝

❝ Compared with SAS this is a "Schnäppchen".


Indeed. Update on the price (a German friend asked for a quotation last July):

Description                  License type   USD per client
PKXpress                     Professional   4,000
(Pharmacokinetic Software)                  (Four Thousand Dollars Only) [sic]

The above price includes:

  1. License cost and installation help remotely.
  2. Initial training of 2 day.

Yearly support Charges will be @ 25% of the License cost per client. The YSS will be applicable from the 2nd year from the date of installation.


❝ It's a nightmare to answer to some posters which have mastered the (list)(/list) construct in between the list points, especially if the list is also hierarchical. And some posters are using this to the excess ;-).


Terribly sorry. Besides Shuanghe I guess you are talking about the forum’s admin, right? :-D
My reason for using list, indents, etc.: I love semantics. Semantically there is a difference between
  • foo
  • bar
or
  1. foo
  2. bar
and

1. foo
2. bar


❝ Is there a way to simplify matters?


Realistically – no. You see similar effects in other boards/forums when replying as well. Here the quoted text (starting with » ) consist of the block-element <pre></pre> which contains an inline child-ele­ment <cite></cite> (hey, seman­tics!). Lists within this element are not allowed. Breaking of list-BB­Codes in a reply is a side-effect of how they are processed in the PHP-script (tries hard to pro­duce valid HTML). Theoretically it would be possible to use <blockquote></blockquote> (which can con­­tain other block-elements). Would mean a major rewrite of the scripts. Not in the near future.
In sophisticated forums (like the SelfHTML Forum) it is possible to use plain HTML-tags instead of BB­Codes. Then the structure will be kept in the reply. But:
  • Users have to know HTML. If they use wrong tags or screw up the nesting the page will not be valid any more. If a page is not valid the browser has to “guess” what might have been meant. Can work in browser A and show only a blank page in browser B.
  • Nasty things are possible in HTML (JavaScript- or even SQL-injections). Needs careful automatic inspection and cleaning of code. The technical background is demanding. Nothing for a hobby-coder like me.

❝ I struggle since hours with an answer post to Yours.


Sorry. Next time don’t worry. I can edit your post.
[image]
A suggestion (if you are using Firefox):
I use the Add-on It’s All Text! for many years. It provides a small button next to the textarea which opens an editor:

You can configure it to your needs:

[image]


I use Notepad2 as editor. It takes two clicks to get rid of the list-BBCodes and replace the [*] with something else:

[image]


❝ Another wish: If I adapt the edit area to greater dimensions and press than PREVIEW it shrinkens to it's standard size. Is it possible to change this behavior?


That’s not possible very, very difficult. The (X)HTML 1.0 standard on this site (and the current HTML 5 as well) require that the <textarea>-tag has attributes for width and height. The con­struct is <textarea cols="xx" rows="yy" name="foo" id="bar"></textarea> where xx and yy are the number of mono­spaced characters (were 78 and 25; changed to 95 and 30). These attributes are mandatory since users may have their own style-sheet or switched off CSS completely. The forum’s stylesheet already con­tains the CSS 3.0 property

textarea {
  resize: both;
}

You are lucky because your browser is able to resize the textarea (bloody IEs* can’t…). But since that happens in the client, the server does not “know” that when deli­vering the page again (in the default width).
One wild possibility would be to wrap the textarea with JavaScript, calculate the current width relative to the viewport’s from the respective DOM-nodes, send the information to the server when you click Preview, the server modifies the <cols>-attribute in the deli­vered HTML and (optionally) saves the information in a cookie. Tough job.

  • If you are using IE: Sorry folks – get a CSS 3.0-compliant browser! In IE it would require a Java­Script-library like jQuery to simulate this property. I will not force the ~90% of our users who don’t use IE to download such a monster.
—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

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Ohlbe
★★★

France,
2015-10-11 01:15
(3480 d 17:52 ago)

@ Helmut
Posting: # 15547
Views: 13,419
 

 OT: list limbo and (X)HTML

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Dear Helmut,

❝ Semantically there is a difference between [...]



Really ? Well, I do see a difference between
  • foo
  • bar

and
  1. foo
  2. bar

But I must say that I have some difficulties to see a significant difference between
  1. foo
  2. bar

and

1. foo
2. bar


;-)
—
Regards
Ohlbe
 
Helmut
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Homepage
Vienna, Austria,
2015-10-11 02:01
(3480 d 17:06 ago)

@ Ohlbe
Posting: # 15548
Views: 13,850
 

 OT: list limbo and (X)HTML

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Dear Ohlbe,

❝ But I must say that I have some difficulties to see a significant difference between […]



My first example was/is is an ordered list
  1. Lorem ipsum dolor sit amet, an pro magna complectitur. Ne admodum fuisset sententiae vix, cum ea blandit nominati, minim consul concludaturque qui et. Sit ei vidisse copiosae, quis lu­dus ex sed. Docendi consulatu sententiae usu eu.
  2. Ad eam nostro moderatius, diceret habemus sit no. An laoreet maiestatis sea, nam vivendo epicurei facilisis at. Omnis definitionem ex qui, an dicant ocurreret inciderint qui. Ut graeco fierent epicurei vix, sit no saepe nonumes insolens. Vix ne unum errem.
And the second one two intended paragraphs with numbers at the beginning:

1. Agam eripuit temporibus ut qui, cum ne reque platonem disputando. Euismod propriae adipisci mea id. Quo eu tacimates sen­se­rit, prima falli reprimique an eum. Ut pri vero delenit. Usu illum zril putant at.
2. Claritas est etiam processus dynamicus, qui sequitur mutationem consuetudium lectorum. Mirum est no­­ta­re quam littera go­thica, quam nunc putamus parum claram, anteposuerit litterarum formas huma­ni­ta­tis per seacula quarta decima et quinta de­ci­ma. Eodem modo typi, qui nunc nobis videntur parum clari, fi­ant sollemnes in futurum.


Apart from the ugly typography in the second case search engines treat the semantics differently. In the first case there is an order (look at the HTML-source: <ol></ol>), whereas in the second there is none. In other words, the first list item will be given more weight. Correct, there is an order 1→2→… If you want to have equal weights of the items, an unordered list (<ul></ul>) is the better choice.

Τυπογραφία είναι η τέχνη της αποτύπωσης γραπτού λόγου και εικόνων σε χαρτί, ύφασμα, μέ­ταλλο ή άλλο υλικό με τη βοήθεια τεχνικών μέσων και συνήθως σε μα­ζι­κή κλίμακα.
    Η τυπογραφία ξεκίνησε ουσιαστικά τον 15ο αι. με την εφεύρεση του επίπεδου πι­εστη­ρίου από τον Γουτεμβέργιο. Μέχρι τα τέλη του 20ού αι., η παραδοσιακή τυ­πο­γρα­φία χρη­σι­μο­ποιού­σε κινητά στοιχεία σε διάφορα μεγέθη και οικογένειες (γραμ­μα­τοσειρές) φτιαγμένες από μέταλλο και σπα­νιότερα από ξύλο. Τα στοιχεία αυτά έμπαιναν σε ειδικές θήκες, τους σελιδοθέτες, και κατόπιν στο πιεστήριο για την εκτύ­πωση.
    Στη σύγχρονη στοιχειοθεσία, οι φωτογραφικές διαφάνειες και η λιθογραφία σε με­ταλλικά φύλλα (όφσετ) αντι­κα­τέσ­τησαν τους σελιδοθέτες, ενώ τα κινητά στοιχεία αντι­κατα­στάθηκαν από ηλεκ­τρο­νι­κές γραμματοσειρές με μεγάλη ποικιλία χαρακ­τή­ρων και απεριόριστα μεγέθη. Πάντως κύριο μηχάνημα της τυπογραφίας — πα­ρα­δοσιακής και σύγχρονης — πα­­ρα­μέ­νει το πι­ε­στήριο, που επι­τρέ­πει τη γρήγορη αναπαραγωγή πολλών αντιγράφων.

Beautiful, isn’t it? :-D
—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
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d_labes
★★★

Berlin, Germany,
2015-10-11 16:55
(3480 d 02:13 ago)

@ Helmut
Posting: # 15550
Views: 13,277
 

 OT: list limbo and (X)HTML

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Dear Helmut,

many thanks for trying to educate me about the technical foundations of the forum.
But since I doesn't deal with such matters up to now I understood nearly nothing. Only that things are not as easy as they seem. As nearly always in life :cool:.
—
Regards,

Detlew
 
Helmut
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Vienna, Austria,
2015-10-09 15:16
(3482 d 03:51 ago)

@ yjlee168
Posting: # 15542
Views: 13,850
 

 JGuiB

Post reply
Dear Yung-jin,

❝ I assume that you want do following: […]

❝

❝     1. to obtain PK parameters first from your single-dose Ct;


Sorry for not mentioning PkFit since Detlew wrote

❝ ❝ Best would be without some compartment model fit (NCA).


❝ Freeware includes Boomer or ADAPT (required FORTRAN compiler).


I love Boomer. For people not being comfortable with working in a command window / shell I recom­mend your JGuiB.
—
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