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The following message was posted to: PharmPK
Dear All,
We are doing Pharmacokinetics of a compound at two different oral
doses (100 & 200 mg/kg) in rats. We have linear relationships
withrespect to Dose and AUCs. Also other PK parameters calculated
by NCA are comparable.
The plasma profile showed two Cmax, 1 and 2. The observations are
as follows:
1. Cmax1 was 5 times higher than Cmax 2 at 100 mg/kg.
2. Cmax1 was 1/2 of Cmax 2 at 200 mg/kg.
3. Cmax1 at 100 mg/kg was two times higher than Cmax1 at
200mg/kg.
4. Cmax2 at 100 mg/kg was ~1/4 of Cmax2 at 200 mg/kg.
5. Tmax1 was observed at 4h and 1h with 100 and 200 mg/kg doses,
respectively.
we will be highly thankful if somebody can provide us with an
explanation for the same.
Thanking you.
Dr. Jawahar Lal
SABARINATH. S
Research Fellow
Pharmacokinetics & Metabolism Division
C. D. R. I.
Lucknow-226001 INDIA
Phone No: 0522-2212411 to 18 Extn 4377/4389
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The following message was posted to: PharmPK
Hello Sabrinath
The differences you observe could be because at high dose you have very
high
local concentrations which will show initial Tmax much faster than at
low
dose. The differences between the Cmax 1 and Cmax 2 between two doses
can be
due to the dissolution which are influenced by the physicochemical
characteristics of your molecule. Based on the Tmax for the second peak
you
can derive more information if you have information like pKa and logP.
But
it is always better if you mention the range of Tmax and Cmax instead of
mean values between various dose groups.
Venkatesh Atul Bhattaram
CDER, FDA.
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