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The following message was posted to: PharmPK
Dear all,
I would like to estimate the pharmacokinetic
parameters for an anesthetic drug administered by a
simultaneous iv bolus (loading dose) + iv infusion
(maintenance dose for 2 hrs). If the 2 doses are
administered at the same time, then the plasma
concentrations measured corresponds to the drug coming
from the bolus plus that coming from the infusion.
What Pk software could help in this case, I have
looked for in three softwares (Siphar*, Ppharm* and
PKfit*) and I didn't find a solution.
Please help me, any input is highly appreciated
Youssef Hijazi
H=F4pital neurologique et neurochirurgicale
UNITE DE PHARMACOLOGIE CLINIQUE
d=E9partement de dosage de m=E9dicaments et de Pharmacocin=E9tique
B.P. Lyon Montchat 69394 Lyon Cedex 03-FRANCE
Tel: 04 72 35 72 45
[Have a look at http://www.boomer.org/c/p1/Ch06/Ch0605.html and
http://www.boomer.org/pkin/soft.html - db]
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[A few replies - db]
From: Daniel Combs
Date: Fri, 10 Aug 2001 14:27:05 -0700
To: david.at.boomer.org
Subject: Re: Estimation of PK parameters from bolus + infusion administration
infusion administration
The following message was posted to: PharmPK
Youssef:
WinNonlin (www.Pharsight.com) has models to do exactly this. There are
likely similar models in Kinetica (www.Innaphase.com) and Scientist
(???).
If you want to rationally choose the safest IV bolus dose to minimize a
huge Cmax, then I recommend a paper by John G. Wagner: "A safe method
for rapidly achieving plasma concentration plateaus" Clinical
Pharmacology and Therapeutics, 1974 (maybe 1975?), vol. 16, no. 4. pp.
691-700.
--
Dan Combs
Clinical and Experimental Pharmacology and Pharmacokinetics
Development Sciences
Genentech Inc.
voice: (650) 225-5847
fax: (650) 225-6452
email: combs.dan.at.gene.com
---
From: Serge Guzy
Date: Fri, 10 Aug 2001 14:42:03 -0700
To: david.-at-.boomer.org
Subject: RE: Estimation of PK parameters from bolus + infusion administration
infusion adm inistration
The following message was posted to: PharmPK
I would use Winnonlin(for rich data) or Winnonmix (sparse data) as they have
this model as an option in their library of models.
Serge Guzy
Head of Pharmacometrics
Xoma
---
From: Paul Hutson
Date: Fri, 10 Aug 2001 16:51:34 -0500
To: david.aaa.boomer.org
Subject: Re: Estimation of PK parameters from bolus + infusion administration
infusion administration
The following message was posted to: PharmPK
ADAPT II will easily do it. Although it (ADAPTII) is free, the
Fortran compiler it requires is not on this side of the lake. DB
suggests Boomer below; it's worth a look.
Paul
[Thanks Paul, I couldn't resist. There is a Boomer .BAT file at
http://www.boomer.org/software/bats/ib0801.sit which fit the data to
the model as I understand it. I used a two compartment model. You
will need good data. Boomer can be downloaded from
http://www.boomer.org/. There is a link to the .BAT file at the
bottom of this page - db]
---
From: "Sam Liao"
Date: Fri, 10 Aug 2001 18:20:43 -0400
To: david.at.boomer.org
Subject: Re: Estimation of PK parameters from bolus + infusion administration
infusion administration
The following message was posted to: PharmPK
Try WinNonlin, model 15, 16 or 17 for one and two compartment model. For
3-compartment, you have to program your own.
But, it can be done.
Best regards,
Sam Liao, Ph.D.
PharMax Research
270 Kerry Lane,
Blue Bell, PA 19422
phone: 215-6541151
efax: 1-720-2946783
---
From: "Dr. Ibrahim Wasfi"
Date: Sat, 11 Aug 2001 06:42:04 +0400
To: david.at.boomer.org
Subject: Re: PharmPK Estimation of PK parameters from bolus + infusion administration
infusionadministration
The following message was posted to: PharmPK
Dear Yousif:
"Adapt II" by D.Z.D'Argenio and A. Schumitzky from Biomedical Simulations
Resource, University of Southern California will solve your problem. You can
get it free from them.
Regards,
Dr. Ibrahim A. Wasfi
Forensic Science Laboratory
P O Box 253, Abu Dhabi
United Arab Emirates
Tel + 4092522
Fax + 4463470
---
From: johnl.-at-.lg.ehu.es
Date: Sat, 11 Aug 2001 15:28:06 GMT
To: david.at.boomer.org
Subject: Re: Fwd: PharmPK Estimation of PK parameters from bolus + infusion administration
The following message was posted to: PharmPK
Dear Dr. Hijazi,
What you have is a single underlying PK system (eg bi o tri compartmental) and
two different types of external forcing. We have used SAAM (www.saam.com) for
the same problem and is indeed among few packages created on the
system paradigm and thus permitting simultaneous and multiple dosing. It is
well documented and validated, user friendly, and flexible.
Best regards,
John
*********************************
John C Lukas, MS, PhD
School of Medicine
Department of Pharmacology
University of the Basque Country
Leioa, Bilbao Spain 48990
tel: +34 946015560
fax: +34 944800128
*********************************
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Dear Uceph,
WinNonlin offers 1- and 2-compartment PK models which support simultaneous
IV Bolus and Infusion inputs. Pharsight also offers a number of programs
whereby academic institutions may purchase our software at reduced cost. For
information regarding how to obtain a copy of this software package, please
contact our inside sales team (sales.-at-.pharsight.com). In the meantime, I
would be delighted to answer any further questions you may have regarding
the capabilities of our product.
Mark R. Lovern, Ph. D.
Pharsight Scientific Support
Phone: +44 (0) 208 323 8402
Mobile: +44 (0) 781 243 0555
FAX: +44 (0) 208 323 8415
Argentum Center
2 Queen Caroline Street
London, England W6 9DX
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The following message was posted to: PharmPK
Youcef,
ADAPT will also handle this situation of a drug administered by a
simultaneous iv bolus (loading dose) + iv infusion. It is available
free. But does require having the FORTRAN compiler software.
See: http://www.usc.edu/dept/biomed/BMSR.
Bert Lum
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The following message was posted to: PharmPK
Dear Youssef,
Kinetica (the product that evolved from Siphar and P-Pharm, recently
integrated into Kinetica 4.0) is able to carry out this type of data
analysis easily. With graphic modeling capabilities within Kinetica, a user
can write a model with IV infusion
with a loading dose(more than 3 compartment model, with linear or nonlinear
elimination) easily.
Free licenses for registered academic institutions are available by
contacting sales.aaa.innaphase.com. Please visit our website www.innaphase.com
for release news on Kinetica 4.0 Population.
Thank you,
Gregory Samoil
Consulting Services Manager
InnaPhase Corporation
Tel: +1.215.299.7400
Fax: +1.215.299.1242
www.innaphase.com
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