Subjects were included in this analysis, they were given oral doses of tipifarnib mg to mg twice a day for fasting episodes Week Executive Committee, followed by a week off or tuned placebo on the same schedule. The subjects were LY315920 again U treatment until disease progression or severe toxicity T occurred. Week bye week schedule was dissolved Hlt, because it is the recommended dose for patients with myeloma Leuk Mie With acute. Patients were treated with tipifarnib included in this analysis if plasma drug concentrations for population pharmacokinetic analysis. Placebo-treated patients were also included in the analysis, as well as those who had a toxicity t assessment at the beginning and throughout the study. Pharmacokinetic analysis of the pharmacokinetic model was previously developed using data from clinical trials. An open model with three chambers with linear elimination from the central compartment was used to describe the pharmacokinetics of tipifarnib in plasma after intravenous Water infusion.
Tipifarnib was systemically available from the K Body of the fa T linearly one that influenced by the concentration of total bilirubin Was removed. The volume of the central compartment was directly related to the K Correlated body weight. Oral absorption was lodgment as zero order input sequential compartment, by the first order absorption compartment lodgment in the systemic Elesclomol circulation following, and latency models. Since Bev POPULATION showed inter-and intra subject on the pharmacokinetics and the pharmacokinetic parameters were invariant in stable condition w During the first treatment cycle obtained for calculating exposure variables used in the statistical analysis presented here.
Who for any topic Tipifarnib u, of the individual pharmacokinetic parameters were calculated from the Bayesian Sch Estimates of RND Lligen effects calculated with the final Sch Estimates of the parameters of a population pharmacokinetic model to the prior information and the data tipifarnib plasma concentrations. Stage V. NONMEM software was used to calculate individual pharmacokinetic parameters. Table summarizes the sample are included in this analysis in any clinical studies. Tipifarnib plasma concentrations were measured using either high performance liquid chromatography with UV detection or liquid chromatography with tandem mass spectrometry. A study of cross-validation between the two techniques are best for consistency and interchangeability CONFIRMS.
The lower limit of quantification of the UV HPLC and LC MS MS method was. and. ng ml was lower, the mean coefficient of variation in total. over the entire range of concentrations, validates the h forth ng ml. N Here information about the methods were ffentlicht ver. The AUC of tipifarnib in the steady state w During the first treatment cycle was determined by the expression of Fabs ? DAvg CL, where CL and Fab are the Bayes Sch Estimates repr the absolute bioavailability and systemic clearance and DAvg Presents the average dose twice t Possible for each patient w During the first treatment cycle tipifarnib administered the therapy, taking into account the respect and or missing doses w tipifarnib during the first treatment cycle. EMI average iinn : DAvg was calculated from the following equation