effectiveness of highly variable drugs [Off Topic]

posted by Dr_Dan  – 2013-12-18 08:34 (2426 d 20:34 ago) – Posting: # 12070
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Dear Ken
Please keep in mind that the active metabolite of clopidogrel which was demonstrated to be linearly related to the AUC of clopidogrel is not as variable as the parent drug and within the systemic circulation the active metabolite is about 5000-fold higher than the inactive parent drug. In consequence high variability in PK parameters of the parent drug do not necessarily lead to high variability in therapeutic outcome. The limiting step for maximal effect of clopidogrel is not bioavailability but biotransformation (see Savi P, Herbert JM: Clopidogrel and ticlopidine: P2Y12 adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis. Semin Thromb Hemost. 2005; 31: 174-83).
Kind regards
Dan

Kind regards and have a nice day
Dr_Dan

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