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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
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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
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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.
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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.
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