Table of Contents

Abstract: Powder flow is influenced by environmental factors, such as moisture and static electricity, as well as powder related factors, such as morphology, size, size distribution, density, and surface area. Pharmaceutical solids may be exposed to water during storage in an atmosphere containing water vapor, or in a dosage form consisting of materials (e.g., excipients) that contain water and are capable of transferring in to other ingredients. The effect of moisture on powder flowability depends on the amount of water and its distribution. The aim of this work was to examine the effect of humidity on the flow properties of theophylline using information derived from solid-state analysis of the systems investigated.

Abstract: Tacrolimus is a calcineurin inhibitor immunosuppressant that has seen considerable use in both adult and pediatric solid organ transplant recipients. Though there is much pharmacokinetic data available for tacrolimus in the adult population, the literature available for children is limited. Furthermore, very little is known about the pharmacogenomic differences in the two patient groups. Based on what information is currently available, clinically significant differences may exist between the two populations in terms of absorption, distribution, metabolism and elimination. In addition, inherent physiological differences exist in the young child including: less effective plasma binding proteins, altered expression of intestinal P-glycoprotein, and increased expression of phase 1 metabolizing enzymes, therefore one would expect to see clinically significant differences when administering tacrolimus to a child. This paper examines available literature in an attempt to summarize the potential pharmacokinetic and pharmacogenomic variability that exists between the two populations.

Abstract: This study investigated gene expression of drug resistance factors in biopsy tissue samples from hepatocellular carcinoma (HCC) patients undergoing chemotherapy by platinum complex. Liver biopsy was performed to collect tissue from the tumor site (T) and the non-tumor site (NT) prior to the start of treatment. For drug-resistant factors, drug excretion transporters cMOAT and MDR-1, intracellular metal binding protein MT2, DNA repair enzyme ERCC-l and inter-nucleic cell transport protein MVP, were investigated. The comparison of the expression between T and NT indicated a significant decrease of MT2 and MDR-1 in T while a significant increase in ERCC-1 was noted in T. Further, expression was compared between the response cases and non-response cases using the ratios of expression in T to those in NT. The response rate was significantly low in the high expression group when the cutoff value of cMOAT and MT2 was set at 1.5 and 1.0, respectively. Furthermore, when the patients were classified into A group (cMOAT ≧ 1.5 or MT2 ≧ 1.0) and B group (cMOAT < 1.5 and MT2 < 1.0), the response rate of A group was significantly lower than B group when we combined the cutoff values of cMOAT and MT2. It is considered possible to estimate the therapeutic effect of platinum complex at a high probability by combining the expression condition of these two genes.

Abstract: Application of oral fast release amantadine and levodopa may induce an improvement of motor symptoms in patients with Parkinson’s disease (PD). The objective of this trial was to investigate the clinical efficacy of a fast release amantadine sulfate formulation on simple and complex movement performance and putative relations to the pharmacokinetic behavior in PD patients. We challenged two cohorts of 12 PD patients, who were taken off their regular antiparkinsonian treatment for at least 12 hours, with oral 300 mg amantadine sulfate. We scored motor symptoms and performed instrumental tasks, which ask for performance of simple or complex motion series under cued conditions. Motor symptoms and performance of complex movements significantly improved in contrast to the carrying-out of simple motions. N-methyl-D-aspartic acid antagonistic and dopaminomimetic amantadine also influences altered higher predominant prefrontal cognitive functions. Therefore, performance of complex motion series improved, whereas carrying-out of simple repetitive movements is more associated to the striatal dopamine dependent basal ganglia function.