Evaluation of the bioequivalence of tablets and capsules containing the novel anticancer agent R115777 (Zarnestra) in patients with advanced solid tumors

M. Crul, G. J. De Klerk, M. Swart, L. Weiner, P. A. Palmer, C. J. Bol, J. H. Beijnen, J. H.M. Schellens

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R 115777 (Zarnestra) is a novel anticancer agent, currently undergoing phase III clinical testing. An open, cross-over trial was performed in 24 patients with solid tumors to compare the bioavailability of a new tablet formulation with the standard capsule formulation. Both dosage forms were administered once daily in doses of 300 or 400 mg. Patients received R115777 as a capsule on day 1 and as a tablet on day 2, or vice versa. Blood samples were drawn up to 24 hours after drug intake and R115777 levels were measured using a validated high performance liquid chromatography (HPLC) method. The following pharmacokinetic parameters were determined and compared for the two formulations: time to maximal plasma concentration (Tmax), half-life (t1/2), maximal plasma concentration (Cmax) and area under the curve at twenty-four hours (AUC24h). For the latter two parameters, 90% classical confidence intervals of the ratio tablet/capsule were calculated after a log-transformation, using an Analysis of Variance (ANOVA). For t1/2 and Tmax, no statistically significant differences were found between tablet and capsule. The point estimates of the ratio's of the log-normalized Cmax and AUG24h were 0.94 and 0.92, respectively, and the 90% confidence intervals were 0.81-1.09 and 0.83-1.03, which is within the critical range for bioequivalence of 0.80-1.25. In conclusion, the established pharmacokinetic parameters demonstrate that the capsule and tablet formulations of R115777 are interchangeable.

Original languageEnglish
Pages (from-to)61-65
Number of pages5
JournalEuropean Journal of Drug Metabolism and Pharmacokinetics
Issue number1
Publication statusPublished - 1 Jan 2002


  • Anticancer agent
  • Bioequivalence
  • R 115777
  • Solid tumors

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