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

Pharmacokinetics of tipifarnib after oral and intravenous administration in subjects with advanced cancer.

The primary objective of this study was to identify intravenous regimens of tipifarnib that would mimic the systemic exposure obtained after the current twice-daily oral administration of tipifarnib. After determination of an intravenous dose that 6 subjects with advanced cancer could tolerate, another 26 subjects were randomly assigned to receive 3 consecutive 4-day regimens of tipifarnib with different treatment sequences: a 100-mg 2-hour intravenous infusion, 200-mg oral administration twice daily, and a 200-mg/d continuous intravenous infusion. The systemic exposure to tipifarnib was comparable among these 3 regimens. The plasma concentration-time profile of 2-hour intravenous infusion more closely resembled the oral administration than did the continuous infusion. Glu-curonidation is a metabolic pathway for tipifarnib with concentrations of the glucuronide conjugate greatly exceeding the parent compound after oral and intravenous administration. Analysis of plasma metabolites indicated that tipifarnib also undergoes dealkylation and loss of the imidazole group.[1]

References

  1. Pharmacokinetics of tipifarnib after oral and intravenous administration in subjects with advanced cancer. Zhang, S., Zannikos, P., Awada, A., Piccart-Gebhart, M., Dirix, L.Y., Fumoleau, P., Verhaeghe, T., Francois, M., De Porre, P. Journal of clinical pharmacology. (2006) [Pubmed]
 
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