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The following message was posted to: PharmPK
Hello:
I have been working with a drug where the usual dose is around 1g - but
patients often receive a lower dose. In order to compare Cmax and AUC
between patients who received various doses, I and others have adjusted
the Cmax and AUC to a 1g dose. For metabolic ratio, it would seem
intuitive that giving a bigger parent dose, would result in a larger AUC
for metabolite. If the parent is adjusted and the metabolite is not,
the numerator (metabolite) would be considerably small relative to the
adjusted (to 1g) denominator. I have usually just used unadjusted
parent AUC for this calculation to circumvent this issue. However, I am
also reporting a metabolite AUC and Cmax - which I have not "adjusted".
Is that the correct approach? It would seem that if one simply viewed
the values for these terms, the AUC and Cmax would be considerably
smaller than for an adjusted value used the parent. Perhaps I should
also report unadjusted AUC and Cmax for Parent??
I look forward to hearing some of your opinions.
Melanie Joy
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The following message was posted to: PharmPK
Hi Melanie,
It is difficult to adjust metabolite exposure to a 1g dose, because
molecular weight is generally different between the parent drug and its
metabolite. Why don't you think using 1mol dose for adjustment? I
think it might be smart handling.
Best regards,
Mitsuo Higashimori
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