MGR
★

India,
2007-02-02 11:10
(5899 d 22:55 ago)

Posting: # 502
Views: 38,674

## IVIVC Studies [Dissolution / BCS / IVIVC]

Dear all,

Please tell me about how to proceed for IVIVC using the pilot data. Also can anybody tell me the important tests and procedure for IVIVC Studies using WinNonlin or any software (SAS, SPSS,.....). If there are any important sites regarding IVIVC kindly let me know.

Thanks and regards,
MGR

Regards,
MGR
Helmut
★★★

Vienna, Austria,
2007-02-07 20:56
(5894 d 13:10 ago)

@ MGR
Posting: # 510
Views: 38,140

## IVIVC Studies

Dear Mamidi!

❝ Please tell me about how to proceed for IVIVC using the pilot data.

OK, you are going in the right direction, namely starting with in vivo data!

❝ Also can anybody tell me the important tests and procedure for IVIVC Studies using WinNonlin or any software (SAS, SPSS,.....).

Unless you want to start with parametric deconvolution, even M$-Excel will do the job (I would not trust the built-in Solver-routine)… Kinetica offers templates for the ‘classical’ methods (Wagner-Nelson, Loo-Riegelman) and convolution/deconvolution. If you have already a little experience with WinNonlin’s programming language, it should not be too difficult to implement any needed model manually. An additional product (the IVIVC Tookit) is available for the latest release (5.2) of WinNonlin only. ❝ If there are any important sites regarding IVIVC kindly let me know. Not directly IVIVC, but browse through the archive at Dissolution Technologies, and have a look at this nice review. 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 venu ☆ Mumbai, India, 2007-02-23 07:58 (5879 d 02:08 ago) @ Helmut Posting: # 533 Views: 35,989 ## IVIVC Studies Dear HS! I would like to share this piece of infomation which I am sure will be useful: http://www.dissolutiontech.com/DTresour/800Articles/800_art1.html Best Regards, Vandana Panchal Best Regards, Ms. Vandana Panchal Biostatistician Mumbai India Dipesh Jayswal ● 2007-03-16 08:53 (5858 d 01:12 ago) @ venu Posting: # 582 Views: 35,656 ## IVIVC Studies Dear groupmates, can u please suggest the method for calculating "dose absorbed" at each sampling time point from Plasma concentration Vs Time profile of the subject from Bioequivalence study? Please suggest me the complete procedure with formula or some easily accessible reference on net. Thanks in advance, Dipesh Jayswal Helmut ★★★ Vienna, Austria, 2007-03-16 16:39 (5857 d 17:26 ago) @ Dipesh Jayswal Posting: # 583 Views: 37,841 ## Wagner-Nelson, Loo-Riegelman Dear Dipesh! First of all get the two ‘classical’ papers; for the 1-compartment model,[1] and for the 2-compartment model.[2] ❝ Please suggest me the complete procedure with formula… Below is a simple example of the Wagner-Nelson method. 1. Estimate kel from t=15 to t=32: 0.1271 2. Calculate the partial AUCs (column 3) 3. Calculate amount excreted / central volume of distribution: column 4 = column 3 x kel 4. Calculate amount absorbed / central volume of distribution: column 5 = column 2 + column 4 5. Calculate %absorbed: column 6 = column 5 / asymptotic plateau (estimated as mean from t=15 to t=32: 9.976)  ┌────┬──────┬───────┬───────┬───────┬──────┐ │ c1 │ c2 │ c3 │ c4 │ c5 │ c6 │ ├────┼──────┼───────┼───────┼───────┼──────┤ │ t │ C(t) │ AUC(t)│ Ae/Vp │ Aa/Vp │ %abs │ ├────┼──────┼───────┼───────┼───────┼──────┤ │ 0 │ – │ – │ – │ – │ 0.00 │ │ 1 │ 2.28 │ 1.14 │ 0.14 │ 2.42 │ 0.24 │ │ 2 │ 3.69 │ 4.13 │ 0.52 │ 4.21 │ 0.42 │ │ 3 │ 5.52 │ 8.73 │ 1.11 │ 6.63 │ 0.66 │ │ 4 │ 5.52 │ 14.25 │ 1.81 │ 7.33 │ 0.73 │ │ 5 │ 5.08 │ 19.55 │ 2.49 │ 7.57 │ 0.76 │ │ 6 │ 4.91 │ 24.55 │ 3.12 │ 8.03 │ 0.80 │ │ 8 │ 4.10 │ 33.56 │ 4.27 │ 8.37 │ 0.84 │ │ 10 │ 3.38 │ 41.04 │ 5.22 │ 8.60 │ 0.86 │ │ 12 │ 3.33 │ 47.75 │ 6.07 │ 9.40 │ 0.94 │ │ 15 │ 2.66 │ 56.73 │ 7.21 │ 9.87 │ 0.99 │ │ 24 │ 0.80 │ 72.30 │ 9.19 │ 9.99 │ 1.00 │ │ 28 │ 0.49 │ 74.88 │ 9.52 │ 10.01 │ 1.00 │ │ 32 │ 0.31 │ 76.48 │ 9.72 │ 10.03 │ 1.01 │ └────┼──────┼───────┴───────┼───────┼──────┘ │0.1271│ │ 9.976│ └──────┘ └───────┘ ❝ … or some easily accessible reference on net. A nice website is run by David Bourne. If you want to examine your own data you will need the Java-plugin for your browser; for examples on absorption see this one of David's pages and followings. 1. Wagner JG, Nelson E. Per Cent Absorbed Time Plots Derived from Blood Level and / or Urinary Excretion Data. J Pharm Sci. 1965; 52: 610–1. 2. Loo JCK, Riegelman S. New Method for Calculating the Intrinsic Absorption Rate of Drugs. J Pharm Sci. 1968; 57: 918–28. 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 Dipesh Jayswal ● 2007-03-19 11:04 (5854 d 23:01 ago) @ Helmut Posting: # 586 Views: 36,425 ## Wagner-Nelson, Loo-Riegelman Dear HS, Thanks a lot for ur detailed calculation. Regards, Dipesh drcampos ★ Brazil, 2007-03-19 16:26 (5854 d 17:39 ago) @ Helmut Posting: # 587 Views: 35,733 ## Deconvolution Dr. Helmut, I have just seen your explanation about Wagner-Nelson and Loo-Riegelman methods (model dependent approach). So, if possible, I would like to know how apply deconvolution approach to obtain fraction absorbed using excel. This method is known as model-independent approach. Could you help me with details about calculations and articles about this topic? best regards, Daniel Rossi de Campos Brazil Helmut ★★★ Vienna, Austria, 2007-03-19 17:20 (5854 d 16:46 ago) @ drcampos Posting: # 588 Views: 39,389 ## Numerical Deconvolution Dear Daniel! ❝ So, if possible, I would like to know how apply deconvolution approach to obtain fraction absorbed using excel. This method is known as model-independent approach. Could you help me with details about calculations and articles about this topic? First I would recommend two other ‘classical’ papers: 1. Vaughan DP, Dennis M. Mathematical Basis of Point-Area Deconvolution Method for Determining In Vivo Input Functions. J Pharm Sci. 1978; 67: 663–5. 2. Langenbucher F. Numerical Convolution/Deconvolution as a Tool for Correlating in Vitro with in Vivo Drug Availability. Pharm Ind. 1982; 44(11): 1166–72. Deconvolution is not necessarily model-independent; there are two versions: 1. A model-dependent version, where models are defined for the functions, and the convolution integral solved for the unknown function by means of Laplace Transformations. Unfortunatelly the integral may be impossible to solve… 2. A model-independent version, where the data are deconvoluted numerically, i.e. differentials are replaced by differences. You also might get an impression by an M$-Excel-sheet I prepared, which uses an example from Langenbucher (in German and out of print)…

Langenbucher F. In vitro Prüfung und Korrelation mit in vivo Daten. In: Meier J, Rettig H, Hess H. Biopharmazie – Theorie und Praxis der Pharmakokinetik. Stuttgart 1981; Georg Thieme: pp 300–3.

Main problems with numerical deconvolution are:
Sampling points of the response function (e.g., an oral formulation), and the weighting function (i.e., an i.v. dose or an oral solution) must be equidistant, which they almost never are. Therefore you must interpolate ‘missing’ data points by a suitable algorithm (first approximation would be linear interpolation until Tmax, and linear/log afterwards, better options are splines or Lagrange-polynoms).
Numerical deconvolution is subject to instability such as sudden oscillations in the input function. Errors in early time points have a cumulative effect upon subsequent estimates.

You may use my speadsheet as some kind of a sandbox: alter values, and watch…

For the application of M$-Excel in IVIVC have a look at Langenbucher F. Handling of computational in vitro/in vivo correlation problems by Microsoft Excel: III. Convolution and deconvolution. Eur J Pharm Biopharm. 2003; 56(3): 429–37. doi:10.1016/s0939-6411(03)00140-1. Software packages having a deconvolution module onboard (WinNonlin 5.2+, Kinetica, PDx-IVIVC) rely heavily on smoothing of data – but manufacturers rarely document the actual method in the manual. Good look! 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 drcampos ★ Brazil, 2007-03-19 22:17 (5854 d 11:49 ago) @ Helmut Posting: # 589 Views: 35,844 ## Numerical Deconvolution Helmut, Thank you for your prompt reply and the excel-sheet with detailed calculation. Therefore, the articles suggested and the explanation were very important to understand the principle of the numerical deconvolution. I have just requested the IVIVC module of WinNonlin to Pharsight. Best regards, Daniel Rossi de Campos Brazil Rayhope ☆ India, 2021-10-07 16:25 (538 d 18:40 ago) @ Helmut Posting: # 22621 Views: 3,155 ## Numerical Deconvolution ❝ You may use my speadsheet as some kind of a sandbox: alter values, and watch… Dear Daniel, Is your excel sheet still available to start with? it will be great if you can share it. Regards, Ray. Helmut ★★★ Vienna, Austria, 2021-10-07 18:38 (538 d 16:27 ago) @ Rayhope Posting: # 22622 Views: 2,974 ## Daniel still active in the Forum? Hi Ray, ❝ Is your excel sheet still available to start with? it will be great if you can share it. If you would have looked at Daniel’s profile, you would have noticed that the last time he logged in was nine years ago. You can try to send him a PM. No idea whether the email he used in registration is still current. If that doesn’t work, I can ask him (my last contact was in April). 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 Rayhope ☆ India, 2021-10-08 11:07 (537 d 23:59 ago) @ Helmut Posting: # 22623 Views: 2,878 ## Daniel still active in the Forum? ❝ If you would have looked at Daniel’s profile, you would have noticed that the last time he logged in was nine years ago. You can try to send him a PM. No idea whether the email he used in registration is still current. ❝ If that doesn’t work, I can ask him (my last contact was in April). Sure I will ask Daniel. Thank you. Rayhope ☆ India, 2021-11-11 09:35 (504 d 00:31 ago) @ Rayhope Posting: # 22671 Views: 2,353 ## Daniel still active in the Forum? ❝ ❝ If that doesn’t work, I can ask him (my last contact was in April). Hi, I tried to contact Daniel but I guess not active here. Can you ask him please. Dipesh Jayswal ● 2007-03-21 09:21 (5853 d 00:44 ago) @ Helmut Posting: # 590 Views: 36,003 ## Wagner-Nelson Dear HS, Please correct the year of the publication which u have prescribed in ur mail. 1. Wagner JG and E Nelson; Per Cent Absorbed Time Plots Derived from Blood Level and / or Urinary Excretion Data. J Pharm Sci 52, 610-611 (1963) I hope it will help to locate it for future readers. Regards, Dipesh Helmut ★★★ Vienna, Austria, 2007-03-21 13:13 (5852 d 20:53 ago) @ Dipesh Jayswal Posting: # 591 Views: 35,608 ## Wagner-Nelson Dear Dipesh, oops, thank you for the correction! 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 jesse08 ● 2007-09-01 03:38 (5689 d 07:27 ago) @ Helmut Posting: # 1045 Views: 35,093 ## IVIVC Hi: Anyone know how to calculate the plasma profile using in vitro dissolution profile and IVIVC? i.e. in vivo absorption profile -> plasma profile Thanks. HMY Helmut ★★★ Vienna, Austria, 2007-09-01 16:49 (5688 d 18:17 ago) @ jesse08 Posting: # 1046 Views: 35,240 ## IVIVC / Mapping Dear HMY! ❝ Anyone know how to calculate the plasma profile using in vitro dissolution profile and IVIVC? Yes. ❝ i.e. in vivo absorption profile -> plasma profile This is the concept of ‘Mapping’. You should have all tools given previously in this thread handy. Once you have an IVIVC established, it’s trivial to calculate in vivo dissolution and therefore predict the plasma profile. What is your question? 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 jesse08 ● 2007-09-02 02:32 (5688 d 08:33 ago) @ Helmut Posting: # 1047 Views: 35,127 ## IVIVC / Mapping ❝ Once you have an IVIVC established, it’s trivial to calculate in vivo dissolution and therefore predict the plasma profile. ❝ What is your question? My question is once I have IVIVC, any software or program I can use to predict in vivo plasma profile (i.e. how to run the convolution? How to run the convolution in WinNonlin?) Thanks. HMY Edit: Full quote removed. Please see this post! [HS] Helmut ★★★ Vienna, Austria, 2007-09-02 14:03 (5687 d 21:03 ago) @ jesse08 Posting: # 1048 Views: 35,391 ## IVIVC / Software Dear HMY! ❝ My question is once I have IVIVC, any software or program I can use to predict in vivo plasma profile (i.e. how to run the convolution? How to run the convolution in WinNonlin?) In WinNonlin you have two options: 1. code it yourself (please refer to the references given) – which would be a cumbersome job, or 2. purchase the IVIVC-Toolkit for WinNonlin (≥5.2). If you own WNL5.2 already, a description is given either in ‘…/programs/Pharsight/WinNonlin/User Docs/WNL Users Guide v5_2.pdf’ (pp 295) or in the online help-system (section ‘The IVIVC Toolkit’). Links to other software are given in this thread; Kinetica has IVIVC-Templates ‘onboard’. 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 jesse08 ● 2007-10-03 04:13 (5657 d 06:52 ago) @ Helmut Posting: # 1150 Views: 36,263 ## IVIVC / Software Hi: Did anyone compare the convolution results (i.e. predicted in vivo concentration profile) between Pharsight's IVIVC toolkit and MS-Excel method by Langenbucher's article: Handling of computational in vitro/in vivo correlation problems by Microsoft Excel: III. Convolution and deconvolution? Are the results similar? I am using the MS-Excel method now to do the convolution. I just want to make sure the IVIVC toolkit will produce the same results. HMY Nirali ★ India, 2007-11-21 13:38 (5607 d 20:28 ago) @ jesse08 Posting: # 1316 Views: 35,097 ## IVIVC / Software Dear HS, I have WinNonlin 5.2 version with IVIVC kit. For IVIVC comparison WinNonlin ask minimum three formulation for comparison. I have only two formulations on hand ! Has WinNonlin any other way to compare two formulations Thanks & Regards, Nirali Helmut ★★★ Vienna, Austria, 2007-11-21 16:25 (5607 d 17:41 ago) @ Nirali Posting: # 1317 Views: 35,080 ## at least 3 formulations for IVIVC Dear Nirali, ❝ I have WinNOnlin 5.2 version with IVIVC kit. How much did the IVIVC Toolkit cost? ❝ For IVIVC comparison WinNonlin ask minimum three formulation for comparison. You will need at least 3 data pairs for any type of linear dependency; this is not a WinNonlin-problem. Just imagine: In a linear regression you estimate two parameters – intercept and slope. With 3 data pairs, you have 1 degree of freedom left. With only 2 data pairs you have no degrees of freedom, or in other words you will always be able to draw a straight line, but getting no information on goodness of fit (coefficient of correlation = exactly one). I have only two formulation on hand ! Oh, that’s bad – no resolution possible, unless you come up with results from a 3rd formulation… 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 Nirali ★ India, 2007-11-22 08:53 (5607 d 01:12 ago) @ Helmut Posting: # 1320 Views: 34,812 ## at least 3 formulations for IVIVC Dear Helmut, Thank you. I will definitely get back to you if i have any query about IVIVC. ❝ How much did the IVIVC Toolkit cost? We purchase WinNonlin IVIVC toolkit in April 2007 and paid 3000$/user/single workstation.

Warm Regards,
Nirali
Helmut
★★★

Vienna, Austria,
2007-11-22 10:53
(5606 d 23:13 ago)

@ Nirali
Posting: # 1323
Views: 34,991

## at least 1 formulation for Level A

Dear Nirali,

yesterday I was too fast in responding.
Of course you need ≥3 formulations only for Level B-C correlations. If you were lucky enough to get a point-to-point correlation (Level A), even one formulation (+iv data) is enough.

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
Nirali
★

India,
2007-11-27 07:05
(5602 d 03:01 ago)

@ Helmut
Posting: # 1335
Views: 34,843

## at least 1 formulation for Level A

Dear Mr. Helmut,

Yes you are right. I have little bit idea about level A correlation. I tried it in Excel using Wagner Nelson method.

But here I am not able to perform IVIVC from WinNonlin due to lack of 3rd formulation. Is Level A correlation possible with WinNonlin? Then how?

Friends, pls do share with me if you have exp of WinNonlin IVIVC.

Thanks & Regards,
Nirali
SDavis
★★

UK,
2009-09-25 11:11
(4933 d 23:54 ago)

@ Nirali
Posting: # 4248
Views: 33,568

## IVIVC / Software

Nirali,

"For IVIVC comparison WinNonlin ask minimum three formulation for comparison"

and I am not sure I see where you get that message - it is recommended to have a minimum of 3 but you can build one with the you have or even 1, although of course you will have difficulty having confidence to go extrapolate in the PREDICTION tab, but the first 3 stages will work fine, that is IN VITRO fitting, IN VIVO fitting and CORRELATION

Simon
Senior Scientific Trainer, Certara™
https://www.certarauniversity.com/dashboard
https://support.certara.com/forums/
sonu
☆

2009-09-23 10:47
(4936 d 00:19 ago)

@ Dipesh Jayswal
Posting: # 4234
Views: 33,422

## IVIVC set up/ requirements

Dear HS Sir,

Please send me information regarding basic requirements for set up of IVIVC department/Laboratory?

Regards,
Sonu