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Pharmacokinetic-pharmacodynamic modeling using non-linear mixed effects modeling (NONMEM) is a powerful yet challenging technique, as the software is generally accessed from the command line. A graphical user interface, Piraña, was developed that offers a complete modeling environment for NONMEM, enabling both novice and advanced users to increase(More)
A wide interindividual variability in survival after cancer treatment is observed. This is attributable to many factors, including tumour and patient related factors. Genetic polymorphisms in drug metabolising enzymes and drug transporters may be one of these factors. Drug metabolising enzymes are responsible for the activation, inactivation and(More)
The pharmacokinetics of miltefosine in leishmaniasis patients are, to a great extent, unknown. We examined and characterized the pharmacokinetics of miltefosine in a group of patients with Old World (Leishmania major) cutaneous leishmaniasis. Miltefosine plasma concentrations were determined in samples taken during and up to 5 months after the end of(More)
PURPOSE The anticancer agent, cyclophosphamide, is metabolized by cytochrome P450 (CYP), glutathione S-transferase (GST) and aldehyde dehydrogenase (ALDH) enzymes. Polymorphisms of these enzymes may affect the pharmacokinetics of cyclophosphamide and thereby its toxicity and efficacy. The purpose of this study was to evaluate the effects of known allelic(More)
BACKGROUND The authors assessed the impact of germline polymorphisms on clinical outcome in patients with advanced nonsmall cell lung cancer (NSCLC) who received platinum-gemcitabine (PG) chemotherapy. METHODS In total, 137 patients with stage IIIB/IV NSCLC were included who received first-line PG chemotherapy (74% of patients received cisplatin, and 26%(More)
The key strategy for coping with elevated brain ammonia levels in vertebrates is the synthesis of glutamine from ammonia and glutamate, catalyzed by glutamine synthetase (GSase). We hypothesized that all four GSase isoforms (Onmy-GS01-GS04) are expressed in the brain of the ammonia-intolerant rainbow trout Oncorhynchus mykiss and that cerebral GSase is(More)
Monoclonal antibodies (mAbs) have been used in the treatment of various diseases for over 20 years and combine high specificity with generally low toxicity. Their pharmacokinetic properties differ markedly from those of non-antibody-type drugs, and these properties can have important clinical implications. mAbs are administered intravenously,(More)
The purpose of this study was to evaluate the applicability of virtual endoscopy (VE) in the region of the nose and paranasal sinuses on the basis of volume-rendered spiral CT data. Forty-five patients underwent a low-dose spiral CT of the sinuses. The data were transferred to a workstation running software for volume rendering (EasyVision, Philips Medical(More)
HIV-infected individuals usually receive a wide variety of drugs in addition to their antiretroviral drug regimen. Since both non-nucleoside reverse transcriptase inhibitors and protease inhibitors are extensively metabolised by the cytochrome P450 system, there is a considerable potential for pharmacokinetic drug interactions when they are administered(More)
BACKGROUND The aim of this study was to quantitatively assess the effect of anthropometric and biochemical variables and third-space effusions on paclitaxel pharmacokinetics in solid tumor patients. MATERIALS AND METHODS Plasma concentration-time data of paclitaxel were collected in patients with non-small cell lung cancer (n = 84), ovarian cancer (n =(More)