Ed further treatment and patients who were t in the early days for reasons other than Medikamententoxizit Were replaced t excluded. The patient assessment and monitoring of the entire patient history, examination Rperliche k, H dermatology, chemistry, urinalysis, electrocardiogram were performed at baseline and before each treatment cycle. MP-470 K Rperliche investigation, H dermatology and chemistry were also t Resembled assessed and cycle. Audiometry was performed at baseline and was repeated as clinically indicated. Injury indicators were before treatment, then every two cycles as a basis for assessing the activity of t T measured treatment. All Th toxicity T been classified by the NCI Common Toxicity Criteria version CTC.
Pharmacokinetics Pharmacokinetic studies were carried out for each day of the agent in the first cycle of cisplatin and gemcitabine, and the second cycle. In the second cycle was administered AZD2171 tipifarnib not the day to make a comparison of the pharmacokinetics of gemcitabine and cisplatin with or without tipifarnib erm simultaneous equalization. WW During the cycle, the pharmacokinetic parameters determined tipifarnib day. Blood samples were collected collected for gemcitabine ml min h after the start of infusion w During the cycle and min w ww During cycle minutes. Both gemcitabine and its metabolite deoxy uridine difluoro dFdU were measured in plasma. Each blood sample was centrifuged for tetrahydrouridine ml ml ml mg and for C and g min. Subsequently End end of the layer C in plasma was stored until analysis.
Zus Tzlich blood samples were collected at tzlich ml, and a few hours after the start of infusion of gemcitabine for the determination of gemcitabine triphosphate metabolite dFdCTP Sparidans et al WBC separation was performed using a Ficoll density Pharmacia, Sweden above Heinemann et al Gemcitabine described all levels high performance liquid chromatography was performed using a validated HPLC method analogous to that of Freeman et al. Blood samples were obtained for the cisplatin ml. and h after the start of infusion, blood samples were immediately centrifuged and g C h min. Unbound platinum was equipped with ultrafiltration membranes with YMT Amicon MPS Department kDa, Danvers, MA, USA.
The resulting plasma ultrafiltrate of plasma and total were immediately to analysis by atomic absorption spectrometry AAS AC Van Warmerdam et al stored and hours after start of infusion cisplatin ml was collected white S Blutk Rperchen Blutk S Rperchen measuring adducts of platinum and a delicate test P postlabeling have been validated for the selective determination of Pt and Pt adducts Pluim AG GG et al isolated from blood samples collected at tipifarnib ml, and h after the morning dose immediately after collection, blood samples were centrifuged for C min. The plasma was separated followed from C to analyze the pharmacokinetic limitations by HPLC with UV detection Zujewski et al validated analysis, the following pharmacokinetic parameters recorded using non-compartmental analysis with version WinNonLin company Pharsight, Mountain View, CA, United States: maximum plasma concentration Cmax, the maximum plasma concentration