Dear all.Back to the Top
I have question relating to cmax interpretation in two different
same dose (250mg) but different infusion time in healthy human
In study with 1 hr infusion, the mean Cmax was found to be 2.98 =B5g/ml.
While in other study with 4 hr infusion, the mean cmax was found to be
In 1 hr study, t1/2 was found to be 6.23 +1.07, while in 4 hr infusion
study it was 8.18+ 2.54. The drug follows linear kinetic & parameters
calculated by non-compartmental analysis. In both dose groups, no
change in cl & vd were observed.
Can anyone highlight about how the Cmax reduced to half in 4 hr infusion
study compared to 1 hr infusion time.
Wockhardt Research Centre
Back to the Top
You are putting the same amount of the drug in the system in both
cases. However, when the infusion time is shorter, you reach higher
concentrations because more drug per time unit is coming in. When
infused fast, the amount coming in per time-unit is greater than the
amount being eliminated and thus you see higher concentrations. When
infused slowly, you give the elimination a chance to cope with the
input. In other words, the difference of input to output is smaller
when slower infusion is utilized.
Imagine you are in a bath tub where there is some problems with the
sink. If you open the shower fully, you will soon have the water up to
your knees and will have to shut the shower. However, if you open the
shower at lower pressure, the water might raise to your ankle level
only and you can continue having the crane open. The same amount of
water is used in both cases but the lower pressure (less flow into the
tab per time-unit) allows you to enjoy your bath.
Back to the Top
With respect to your question on Cmax, I agree with the excellent
explanation by Toufigh Gordi. I have an additional comment: The
in Cmax for a 1 and 4 hour-infusion was quite large, assuming that the
dose was the same. In formula, the concentration at the end of the
period is given by
C = Dose/(Tinf*CL)*(1-exp(-k*Tinf))
where Tinf is the duration of the infusion, CL is clearance, and k is
elimination rate constant (=CL/V = 0.693/t1/2).
Given a half-life of about 7 hours (k=0.1), the ratio of Cmax after 1
and after 4 hour is only 1.15, whereas you reported values of 2.98 and
a ratio of about 1.9.
This might be explained by distribution kinetics: if the initial
distribution phase has a half-life of 1.3 hour, one would expect the
reported observed difference in Cmax. Of course this is approximative
assuming a predominant initial distribution phase over 4 hours. Also the
difference in half-life (although probably not significant) may be due
distribution kinetics: the distribution phase is more pronounced after a
shorter infusion, and the reported value for the elimination half-life
be 'disturbed' by distribution, resulting in a shorter value.
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
tel. 31-50 363 3292
fax 31-50 363 3247
Back to the Top
You might want to look at
Mross K, Haring B, Hollander N, Mielke S, Behringer D, Massing U, Unger
Comparison of 1-hour and 3-hours paclitaxel infusion pharmacokinetics:
results from a randomized trial. Onkologie. 2002 Dec;25(6):503-8.
They had very similar observations as to what you described.
Best of luck,
Michael D. Cameron Ph.D.
8609 Cross Park Dr, Suite 100
Austin, TX 78754
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (firstname.lastname@example.org)