Home About us Contact
|
Home About us Contact | ||
|
|
||
Metabolic Transformation (metabolic + transformation)
Selected AbstractsPhysiological effects in juvenile three-spined sticklebacks feeding on toxic cyanobacterium Nodularia spumigena -exposed zooplanktonJOURNAL OF FISH BIOLOGY, Issue 3 2008J.-P. Pääkkönen Feeding rate, growth and nutritional condition as well as nodularin concentration of juvenile three-spined sticklebacks Gasterosteus aculeatus were assessed in an experimental study where field-collected fish were given a diet of zooplankton fed with toxic Nodularia spumigena for 15 days. Food consumption was higher in N. spumigena bloom conditions compared with the cyanobacterium-free control, but despite this the growth rate of exposed fish did not improve. Control fish and fish fed N. spumigena -exposed zooplankton had higher RNA:DNA ratios and protein content than fish grown in cyanobacterial bloom conditions indicating good nutritional condition and recent growth of fish, whereas in bloom conditions metabolic transformation of nodularin to less toxic compounds may cause an energetic cost to the fish affecting the growth rate of the whole organism. Juvenile three-spined sticklebacks collected from the field contained higher concentrations of nodularin at the beginning of the experiment (mean 503·1 ,g kg,1). After 15 days, the lowest nodularin concentrations in fish were measured in the control treatment, suggesting that fish fed with non-toxic food are able to detoxify nodularin from their tissues more effectively than fish in continuing exposure. [source] Synthesis of the anxiolytic agent [14C] 6-hydroxy-buspirone for use in a human ADME studyJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2007Samuel J. Bonacorsi Jr Abstract A reliable synthesis of 14C labeled 6-hydroxy-buspirone is described. The molecule belongs to a unique class of compounds with the potential for anxiolytic activity. A radiolabeled analog was prepared to support the development of 6-hydroxy-buspirone. Specifically, a labeled variant was designed to meet the requirements of a human adsorption-distribution-metabolism-elimination (ADME) study. Multiple 14C labels were needed to fully track the potential metabolic transformation of the molecule. Labeled 6-hydroxy-buspirone was prepared by oxidation of separately labeled versions of [14C]buspirone. The final product was isolated in reasonable yield with a radiochemical purity of 99.8%. Copyright © 2007 John Wiley & Sons, Ltd. [source] A Generic QSAR for Assessing the Bioaccumulation Potential of Organic Chemicals in Aquatic Food WebsMOLECULAR INFORMATICS, Issue 3 2003Abstract This study presents the development of a quantitative-structure activity relationship (QSAR) for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. The QSAR is derived by parameterization and calibration of a mechanistic food web bioaccumulation model. Calibration of the QSAR is based on the derivation of a large database of bioconcentration and bioaccumulation factors, which is evaluated for data quality. The QSAR provides estimates of the bioaccumulation potential of organic chemicals in higher trophic level fish species of aquatic food webs. The QSAR can be adapted to include the effect of metabolic transformation and trophic dilution on the BAF. The BAF-QSAR can be applied to categorize organic chemical substances on their bioaccumulation potential. It identifies chemicals with a log KOW between 4.0 and 12.2 to exhibit BAFs greater than 5,000 in the absence of significant metabolic transformation rates. The BAF-QSAR can also be used in the derivation of water quality guidelines and total maximum daily loadings by relating internal concentrations of organic chemicals in upper trophic fish species to corresponding concentrations in the water. [source] Effects of woohwangcheongsimwon suspension on the pharmacokinetics of bupropion and its active metabolite, 4-hydroxybupropion, in healthy subjectsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2010Hyunmi Kim WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Woohwangcheongsimwon suspension has traditionally been used for the treatment and prevention of stroke, hypertension, palpitations, convulsions and unconsciousness in various Asian countries. , Woohwangcheongsimwon suspensions showed an inhibitory effect on CYP2B6 activity in vitro. Two terpenoids, borneol and isoborneol, are major constituents of woohwangcheongsimwon suspension, and show a competitive inhibition of CYP2B6 with Ki values of 9.5 and 5.9 µm, respectively. , Bupropion undergoes metabolic transformation to the active metabolite, 4-hydroxybupropion, primarily via CYP2B6 both in vivo and in vitro. It is often used as a CYP2B6 substrate for clinical drug,drug interaction studies. , Drug interactions may occur between woohwangcheongsimwon suspension and bupropion. WHAT THIS STUDY ADDS , Co-administration with woohwangcheongsimwon suspension did not alter the pharmacokinetics of bupropion or its metabolite, 4-hydroxybupropion. , Dosage adjustment of bupropion is unnecessary in patients concomitantly administered the highest recommended daily dose of woohwangcheongsimwon suspension. AIMS To examine the effects of woohwangcheongsimwon suspension on the pharmacokinetics of bupropion and its active metabolite, 4-hydroxybupropion, formed via CYP2B6 in vivo. METHODS A two-way crossover clinical trial with a 2 week washout period was conducted in 14 healthy volunteers. In phases I and II, subjects received 150 mg bupropion with or without woohwangcheongsimwon suspension four times (at ,0.17, 3.5, 23.5 and 47.5 h, with the time of bupropion administration taken as 0 h) in a randomized balanced crossover order. Bupropion and 4-hydroxybupropion plasma concentrations were measured for up to 72 h by LC-MS/MS. Urine was collected up to 24 h to calculate the renal clearance. In addition, the CYP2B6*6 genotype was also analyzed. RESULTS The geometric mean ratios and 90% confidence interval of bupropion with woohwangcheongsimwon suspension relative to bupropion alone were 0.976 (0.917, 1.04) for AUC(0,,) and 0.948 (0.830,1.08) for Cmax, respectively. The corresponding values for 4-hydroxybupropion were 0.856 (0.802, 0.912) and 0.845 (0.782, 0.914), respectively. The tmax values of bupropion and 4-hydroxybupropion were not significantly different between the two groups (P > 0.05). The pharmacokinetic parameters of bupropion and 4-hydroxybupropion were unaffected by woohwangcheongsimwon suspension. CONCLUSIONS These results indicate that woohwangcheongsimwon suspension has a negligible effect on the disposition of a single dose of bupropion in vivo. As a result, temporary co-administration with woohwangcheongsimwon suspension does not seem to require a dosage adjustment of bupropion. [source] | ||||||||||