- On 5 Apr 2004 at 09:59:47, Wendy Putnam (wsputn.-a-.yahoo.com) sent the message
Dear all,

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Given that Vss=CL*MRT for an IV bolus dose, does it follow that for an

extravascular dose, Vss/F = CL/F*MRTsys where MRTsys = (AUMC/AUC)sys =

MRT + MIT?

Thanks,

Wendy - On 6 Apr 2004 at 07:40:36, Nick Holford (n.holford.at.auckland.ac.nz) sent the message

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Wendy,

Sorry but its not that easy to compute Vss/F from AUMC and AUC. A

convention for nomenclature is to refer to MRT (mean residence time) as

being the sum of MDT (mean disposition time) and MIT (mean input time).

MDT refers to the disposition of the molecule due only to distribution

and elimination processes. MIT is controlled by the input process.

Some common parametric equivalences are MIT=0 for a bolus input,

MIT=1/KA for a first order input and MIT=duration of input process for

a zero order input.

If you calculate MRT from AUMC and AUC you can then make a guess at MIT

under the assumption of some input model and derive MDT=MRT-MIT. Given

MDT you can then get Vss/F from CL/F*MDT.

Nick

Nick Holford, Dept Pharmacology & Clinical Pharmacology

University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New

Zealand

email:n.holford.aaa.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556

http://www.health.auckland.ac.nz/pharmacology/staff/nholford/ - On 6 Apr 2004 at 10:44:18, David Bourne (david.aaa.boomer.org) sent the message
[A correction and a few replies - db]

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Maria,

Thanks for pointing out this typo... :-)

You are quite correct the MIT for constant rate input is the mean of

the input duration for each molecule and thus it is at the mid-point of

the input duration.

Nick

--

Dear Nick,

You wrote in reply to Wendy:

"MIT=duration of input process for a zero order input."

Please note that MIT is HALF of the duration of the input process for a

zero

order input.

Best regards,

Hans Proost

Johannes H. Proost

Dept. of Pharmacokinetics and Drug Delivery

University Centre for Pharmacy

Antonius Deusinglaan 1

9713 AV Groningen, The Netherlands

--

Further to the explanations offered by Dr Holford, the MIT for a zero

order

input (eg IV infusion) is more commonly expressed as MIT=T/2, where T

is the

duration of input/infusion.

Brendan Johnson, PhD

UNC/GlaxoSmithKline Pharmacokinetics Fellow

Division of Drug Delivery and Disposition

School of Pharmacy, C.B. #7360 Kerr Hall

University of North Carolina at Chapel Hill

Chapel Hill, N.C. 27599-7360

Phone: + 1 919 966-7144

Fax: + 1 919 966-0197

Email: brendan.johnson.at.unc.edu

--

Nick - I believe the MIT for a zero-order infusion is equal to T/2

where T

is the duration of the infusion.

Regards, Jeff

Jeff Wald, PhD

Clinical Pharmacokinetics/Modeling and Simulation

Neurology and GI

RTP, NC

--

Wendy and Nick,

For an input of zero order the MRT will be half the input time not total

duration of input time. For some other calculations related to this

topic

you may want to refer to:

Straughn AB. Model-independent steady-state volume of distribution.

J Pharm Sci. 1982 May;71(5):597-8

Some of the original equations related to multiple zero order infusion

dose calculations of Vss reported in the literature are incorrect.

Art Straughn, Pharm.D.

Professor and Director

Drug Research Laboratory

University of Tennessee

874 Union Ave

Suite 5P

Memphis, TN 38163

E-mail: ASTRAUGHN.aaa.UTMEM.EDU

Phone: (901) 448-6033

Fax: (901) 448-6940

--

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