In vivo is consistent with the hypothesis that the anti-tumor effect of the interruption of a plurality of downstream effectors derived FTase inhibition. Several studies of the dose-escalation phase in patients with advanced solid tumors t monotherapy orally two tipifarnib Zeitpl interpreted IC-87114 as doing a few days a week for continuous measurement. These studies were designed to determine the maximum tolerated dose and characterize the safety and pharmacokinetics of tipifarnib. These studies showed that the pharmacokinetics of tipifarnib linear at doses up to mg twice tm Possible and allows the measurement of oral bioavailability of LL Solution, capsule and tablet form in patients with cancer.
Little or no zeitabh surveilance-Dependent pharmacokinetics was observed after repeated administration of tipifarnib rapidly absorbed after oral administration, peak plasma concentrations in low plasma tipifarnib h-fa achieved it with bi-exponential is associated, and the H Half Enth Lt with life the phase of the first set, terminal half-life drug exposure wh CI-1040 h Betr. Gt Meanwhile, only a small part of the entire bottle surface Fl under the curve of the plasma concentration as a function of time. Plasma accumulation is minimal, when administered twice per day, which indicates that the first phase of the plasma disposition Tipifarnib surmounted concentration-time profile. The drug is almost completely Bound constantly st Constantly. The plasma protein binding is dependent Ngig independent Dependent. the range of plasma concentrations of drugs ? ?? ? ?g ml ? ?? ? In human plasma tipifarnib is Haupts chlich albumin and, to a lesser extent Bound ? ?? S Ureglykoprotein ?.
Tipifarnib is extensively metabolized in humans. The drug could not be detected in the urine and less than Ngliche anf dose was in the F Indices Invariant ver Recovers changed. In vitro and in vivo showed that phase II metabolism, especially the liver Nglucuronidation by excretion of a major route of elimination is tipifarnib. Additionally Tzlich oxidative deamination N, N-demethylation, oxidation and loss are pathways methylimidazole main phases in the metabolism Tipifarnib in vitro studies have shown that the major CYP involved enzyme PA involved in the metabolism of this compound, and CYPC, CYPA, CYPD CYPC and could play a r all data in the metabolism of tipifarnib on file, Johnson & Johnson Pharmaceutical Research & Development, J JPRD.
In this study, data were collected from clinical studies in healthy volunteers or cancer patients, to investigate the pharmacokinetics of tipifarnib. The objectives of this population pharmacokinetic analysis were threefold: I tipifarnib pharmacokinetics after intravenous and oral formulations, water, water solutions of LL, sch protected capsules and tablets Sch ii model BEV POPULATION Bev pharmacokinetic parameters in healthy subjects and cancer re oivent iii assess the influence of demographic factors and other covariates on the pharmacokinetics of tipifarnib. Methods of patient F rderf s capacity data and study design phase of the eight trials with two healthy volunteers and six adult patients with extensive blood and seven phases