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I have a question regarding PK profile of drug compound. The data
acquired by LC/MS/MS.
PO / dose 10 mg/kg in Rat
Time points: 0, 0.5, 1.5, 3, 6, 24 hrs
Conc. 0, 5.0, 4.11, 3.93, 5.96, 1.38 ug/mL
At 0.5 hr the conc. 5.0 ug/mL then drop in conc. at 1.5 and 3 hrs and
going up at 6 hrs (Tmax). It seems like a non-linear kinetic.
This compound forms acylglucuronide. Four QCs were run and QCs are
within acceptable range. Metabolites and IS are separated enough. Any
thoughts on how PK profile of NSAIDs looks like. Samples were
collected in K2EDTA.
What might be possible reasons for this type of profile?
Thank you and look forward to hearing from you.
Anila
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It seems to me as a double peak,
can be due to extravascular depot or enteropathic cycle. PO sugest
enteropathic, have iv data?
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Dear Anila
It would have been better if you included some time points between
6-24 hour like 8, 10 and 12 hour. From the data you have, the
estimation of 6 hour concentration raises an issue. So, just confirm
whether it was analysed properly and the deviation was less. If all
these are fine, the profile may be an indicative of enterohepatic
circulation.
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