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Dear All,
I have a question about how to correlate the plasma concentration of
drugs which lower plasma glucose level to OGTT (oral glucose
tolerance test) value following a single dose study.
From this paper,
Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4
inhibitor, on incretin and plasma glucose levels following an oral
glucose tolerance test in patients with type 2 diabetes. (J Clin
Endocrinol Metab. 2006 Aug 23; Herman GA et al.)
drug concentrations were correlated to the primary efficacy endpoint,
which was the glucose excursion above the pre-OGTT glucose level over
a 4-hour interval ([incremental AUC0-4 hr] following an OGTT
administration at 2 hrs postdose (see PK/PD assessment section and
table II in the paper). But I don't understand how this is done.
I thought that the drug concentration and drug response needs to be
monitored at the same timeframe so that a concentration-response
graph can be plotted to observe if there is any time delay for PK/PD
assessment purpose.
Thanks in advance,
Yvonne
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The following message was posted to: PharmPK
Dear Yvonne,
> drug concentrations were correlated to the primary efficacy endpoint,
> which was the glucose excursion above the pre-OGTT glucose level over
> a 4-hour interval ([incremental AUC0-4 hr] following an OGTT
> administration at 2 hrs post-dose (see PK/PD assessment section and
> table II in the paper). But I don't understand how this is done.
I do not know this paper, but the approach sounds to be not mechanism-
based.
Perhaps you should have a look at
Gopalakrishnan M, Suarez S, Hickey AJ, Gobburu JV. Population
pharmacokinetic-pharmacodynamic modeling of subcutaneous and pulmonary
insulin in rats.
J Pharmacokinet Pharmacodyn. 2005 Aug;32(3-4):485-500.
D Czock
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