- On 3 Sep 2014 at 10:04:52, GuGary (gary-gu.-at-.OUTLOOK.COM) sent the message

Back to the Top

Dear PharmPK experts,

Recently I saw someone estimated Vss from multiple-dosing data using the equation:

Vss=CLss*T1/2(eff)/Ln(2), where CLss is steady-state clearance obtained by Dose/AUCtau, and

T1/2(eff) is the effective half life obtained from Racc.

It is the first time for me to know this calculation method. Can anybody know whether this equation

is valid? Is there any precondition? Can anybody suggests references for me? To my understanding,

the calculation of T1/2 (eff) is regardless of the PK linearity, but V=CL*T1/2/Ln(2) is derived from

linear PK principle. So I am confused, and doubt the validity of the equation previously mentioned.

In addition, I would like to confirm whether Vss=CL*MRT can be extended to steady state or not, that

is, Vss=CLss*MRTss? In this situation, which kind of MRT should be used as MRTss? To my

understanding, taking parameters given by Phoenix as an example, "MRTlast", which is obtained based

on the C-T profile within a dosing interval at steady state, should be used. Am I right?

Thank you

Gary - On 25 Sep 2014 at 09:02:33, gary-gu.-at-.outlook.com sent the message

Back to the Top

Dear PharmPK experts,

Recently I saw someone estimated Vss from multiple-dosing data using the equation:

Vss=CLss*T1/2(eff)/Ln(2), where CLss is steady-state clearance obtained by Dose/AUCtau, and

T1/2(eff) is the effective half life obtained from Racc.

It is the first time for me to know this calculation method. Can anybody know whether this equation

is valid? Is there any precondition? Can anybody suggests references for me? To my understanding,

the calculation of T1/2 (eff) is regardless of the PK linearity, but V=CL*T1/2/Ln(2) is derived from

linear PK principle. So I am confused, and doubt the validity of the equation previously mentioned.

In addition, I would like to confirm whether Vss=CL*MRT can be extended to steady state or not, that

is, Vss=CLss*MRTss? In this situation, which kind of MRT should be used as MRTss? To my

understanding, taking parameters given by Phoenix as an example, "MRTlast", which is obtained based

on the C-T profile within a dosing interval at steady state, should be used. Am I right?

Thank you

Gary - On 25 Sep 2014 at 15:14:03, Charlie Brindley (charlie.brindley.at.kinetassist.com) sent the message

Back to the Top

Dear Gary,

You could use Vss=CLss*T1/2(eff)/Ln(2) for a one-compartment model after an intravenous bolus dose.

Otherwise, I would steer clear. The limitations of "effective half-life" after extravascular dosing

has been extensively covered in previous PharmPK discussions and is nicely summarised in Sahin and

Benet (Pharmaceutical Research, Vol. 25, No. 12, December 2008).

At steady state, Vss = CLss*MRTss where CLss is Dose/AUC0-tau and MRTss is: [AUMC(0-tau) +

tau*AUC(tau-inf)]/AUC(0-tau).

In WinNonlin Phoenix, if you include a value of tau in "NCA workflow" it assumes steady state

conditions and will calculate MRT and Vss appropriately. (Simon Davies, please can you confirm)!

Best regards,

Charlie

Charlie Brindley, KinetAssist Ltd. - On 30 Sep 2014 at 08:28:33, Simon Davis (Simon.Davis.-at-.certara.com) sent the message

Back to the Top

Yes Charlie that is correct. If you include a value of tau (i.e. your regular dosing interval) in a

Phoenix WinNonlin's NCA object's dosing input, all outputs will be generated with an assumption of

steady-state conditions as per the formulas specified in the help files.

Best regards,

Simon.

Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@lists.ucdenver.edu with "Vss estimation from effective half life" as the subject |

Copyright 1995-2014 David W. A. Bourne (david@boomer.org)