Back to the Top
The following message was posted to: PharmPK
Dear All,
When I was evaluating a compound PK profile in dog after single dose
oral administration in capsules, its C24hr happened to be much higher
compared to C8hr (Cmax at 2-4hr). Dose anyone meet the same problem
before and what could be the potential reason?
Thanks,
Yan
[Do you have any other data, between 8 and 24 hr? - db]
Back to the Top
Hi Yan,
-Do you have IV data?
-What kind of metabolite your compound generate?
-One thing could be happening - drug conjugates excreted in the bile
can be hydrolyzed in the gut and the drug reabsorbed - Entereohepatic
Recirculation.
Regards
Anila
Back to the Top
The following message was posted to: PharmPK
Dear Yan
Though two peaks are observable in the PK profile, yet a higher peak at
24 hour is interesting and unusal. It would be interesting to know that
in what dosage form the drug was administered? Was the tissue
distribution study under taken and what was the trend in betweeen 8 and
24 hours?
Nadeem Irfan Bukhari
Back to the Top
The following message was posted to: PharmPK
All,
Thank for your reply. Just give more details of the study:
1. No time points between C8hr and C24hr.
2. The drug was dosed in 100% water in Gelatine capsule.
3. Same phenomenon was not observed in a crossover study dosing with
100% Water solution at the same dose level.
4. Glucuronide could be the major metabolite.
Yes, Entereohepatic recirculation could be one reason. But could it
happen in such a late time point (24hr), given a Tmax at 2-4hr?
Thanks,
Yan
Back to the Top
Dear Yan
The only culprit here, i guess is the formulation (gelatine caps)
which might have been irregular in the drug release since you are
stating you have not seen the similar kind of profile in crossover
formulation. This can not be attributed to enterohepatic
recirculation as such phenomenon at 24h is questionable. Ensure
method of analysis is perfect and no interference peak is seen at the
RT.
You can perform an in-vitro dissolution study with the formulation to
study its release pattern.
Please clarify if i am wrong...
Back to the Top
Dear all,
If your using gelatin capsule, which is meant for Immediate release
can hold the drug in the formulation max up to 20 mins. Although in
invitro if aged capsule shell have been used it may give some
variation, that doesn't mean that in In vivo especially in presence
of enzyme the crosslinked chain of gelatin break downs and dissovles.
To ensure that please check by testing the capsule's dissolution by
USP teir II method.
Please recheck your study and ensure the analyatical part.
Girish Karanth
Back to the Top
The following message was posted to: PharmPK
Dear Yan,
I have seen this before. What is the drug concentration in
capsules vs water solution? Is it possible that your drug crashes out
in the
capsules and become slowly BA as travels along the GI tract? What is
the dose
volume when you administer the compound as a solution? How do you
administer
the capsules? Do you follow with washout? If yes, what volume of
water was given?
Did all the dogs shows the 24 peak?
Best regards,
Rostam
|
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "C24 higher than C8 in dog PK" as the subject | Support PharmPK by using the |
Copyright 1995-2011 David W. A. Bourne (david@boomer.org)