effectiveness of highly variable drugs [Off Topic]

posted by Ohlbe – France, 2013-12-18 10:07 (2426 d 20:47 ago) – Posting: # 12071
Views: 10,563

Dear Dan,

» [...] within the systemic circulation the active metabolite is about 5000-fold higher than the inactive parent drug.

I had figures in mind of about 2000-fold for the inactive carboxyacid metabolite. The few papers I have seen where the active thiol metabolite (H4) was measured indicate (on a limited population, after repeated administration) a much lower Cmax ratio. I didn't see any information on intra-CV of this metabolite (but I only browsed very quickly through the papers, and did not do an extensive review of litterature).

See these papers for more info:
Makoto Takahashi, Henrianna Pang, Kiyoshi Kawabata, Nagy A. Farid, Atsushi Kurihara
Quantitative determination of clopidogrel active metabolite in human plasma by LC–MS/MS
Journal of Pharmaceutical and Biomedical Analysis 48 (2008) 1219–1224

Marta Karazniewicz-Łada, Dorota Danielak, Artur Tezyk, Czesław Zaba, Gilles Tuffal, Franciszek Główka
HPLC–MS/MS method for the simultaneous determination of clopidogrel, its carboxylic acid metabolite and derivatized isomers of thiol metabolite in clinical samples
Journal of Chromatography B, 911 (2012) 105– 112

Michael T. Furlong, Ishani Savant, Moucun Yuan, Laura Scott, William Mylott, Thomas Mariannino, Pathanjali Kadiyala, Vikram Roongta, Mark E. Arnold
A validated HPLC–MS/MS assay for quantifying unstable pharmacologically active metabolites of clopidogrel in human plasma: Application to a clinical pharmacokinetic study
Journal of Chromatography B, 926 (2013) 36– 41


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