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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Pharmacokinetics of a prodrug thymoxamine: dose-dependence of the metabolite ratio in healthy subjects.

Thymoxamine, a prodrug, is rapidly deacetylated in the plasma to give two phase I metabolites, DMAT and DAT, which are further sulpho- and glucuro-conjugated and then excreted mainly in the urine. In a cross-over study, the dose-dependence of the metabolite ratio was evaluated in nine healthy volunteers after three doses (120, 240, 480 mg) of thymoxamine-HCl. Regardless of the dose, DMAT and its glucuronide were not detected, while the amount of DMAT-sulphate was found to be proportional to the dose administered. Plasma levels of DAT were measurable in only four of the nine subjects after the 480 mg dose and showed great intersubject variability. The pharmacokinetics of both DAT-sulphate and DAT-glucuronide were dose-dependent. As the dose increased, the proportion of DAT undergoing sulphatation decreased; this saturation was compensated by glucuronidation.[1]

References

  1. Pharmacokinetics of a prodrug thymoxamine: dose-dependence of the metabolite ratio in healthy subjects. Marquer, C., Trouvin, J.H., Lacolle, J.Y., Dupont, C., Jacquot, C. European journal of drug metabolism and pharmacokinetics. (1991) [Pubmed]
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