Early phase pharmacokinetics but not pharmacodynamics are influenced by propofol infusion rate

Background: Conventional compartmental pharmacokinetic models wrongly assume instantaneous drug mixing in the central compartment, resulting in a flawed prediction of drug disposition for the first minutes, and the flaw affects pharmacodynamic modeling. This study examined the influence of the administration rate and other covariates on early phase kinetics and dynamics of propofol by using the enlarged structural pharmacokinetic model. Methods: Fifty patients were randomly assigned to one of five groups to receive 1.2 mg/kg propofol given with the rate of 10 to 160 mg . kg(-1) . h(-1). Arterial blood samples were taken frequently, especially during the first minute. The authors compared four basic pharmacokinetic models by using presystemic compartments and the time shift of dosing, LAG time. They also examined a sigmoidal maximum possible drug effect pharmacodynamic model. Patient characteristics and dose rate were obtained to test the model structure. Results: Our final pharmacokinetic model includes two conventional compartments enlarged with a LAG time and six presystemic compartments and includes following covariates: dose rate for transit rate constant, age for LAG time, and weight for central distribution volume. However, the equilibration rate constant between central and effect compartments was not influenced by infusion rate. Conclusions: This study found that a combined pharmacokinetic-dynamic model consisting of a two-compartmental model with a LAG time and presystemic compartments and a sigmoidal maximum possible drug effect model accurately described the early phase pharmacology of propofol during infusion rate between 10 and 160 mg . kg(-1) . h(-1). The infusion rate has an influence on kinetics, but not dynamics. Age was a covariate for LAG time

テンペ脂溶性画分の抗酸化性に関する研究

テンペ水溶性画分の抗酸化性は,未発酵大豆よりも強く,さらにこのテンペを嫌気発酵させたテンペでは抗酸化能が増強されることが報告されている。そこで,脂溶性画分においても強い抗酸化能が得られるかを,エタノール-バッファー系及びβ-カロテンエマルジョン系による抗酸化能の検討で試みた。その結果,テンペ及び嫌気発酵させたテンペの抗酸化性は未発酵大豆より強かったが,テンペと嫌気発酵させたテンペの抗酸化性に差はなかった。Tempe is a traditional fermented soy product native to Indonesia. The purpose of this study was to compare the antioxidant activities in lipid soluble fractions of two kinds of tempes with unfermented soybean by assays using ethanol-buffer and emulsion systems. Lipid soluble fractions were extracted by diethylether from freeze-dried powder of soybean, tempe made by aerobic fermentation of boiled soybean with Rhizopus microsporus, and tempe processed with further anaerobic fermentation. The antioxidant activity of tempe and anaerobic tempe was stronger than that of soybean, although that of tempe was similar to that of anaerobic tempe. These results suggested that tempe and anaerobic tempe might be made available as food for preventing lipid peroxidation in vivo

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens\u27 antibacterial susceptibility

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010.The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents.Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S.aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S.pneumoniae were 1.1% and 0.0%, respectively. Among H.influenzae, 17.6% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be β-lactamase-non-producing ABPC-resistant and 11.0% to be β-lactamase-producing ABPC-resistant strains. Extended spectrum β-lactamase-producing K.pneumoniae and multi-drug resistant P.aeruginosa with metallo β-lactamase were 2.9% and 0.6%, respectively.Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis