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  • 1
    Electronic Resource
    Electronic Resource
    The effect of body weight on dalteparin pharmacokinetics A preliminary study (2000)
    Springer
    European journal of clinical pharmacology 56 (2000), S. 293-297 
    Details
    ISSN: 1432-1041
    Keywords: Key words Dalteparin ; Low-molecular-weight heparins ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Aim: To investigate whether there were significant differences in the volume of distribution (V) and clearance (CL) of dalteparin in obese versus normal-weight patients, and thereby determine whether dosing of dalteparin should be based on total body weight, lean body weight or an adjusted body weight in obese patients. Methods: Patients (ten obese and ten normal weight) treated with dalteparin were matched for age, gender, lean body weight and creatinine CL. Two steady-state plasma dalteparin concentrations were taken from each patient and assayed in duplicate. The pharmacokinetic values of V and CL were estimated, for each patient, using the Bayesian maximum a posteriori method with the program ABBOTTBASE. Results: The mean V in obese patients was approximately 60% larger than in normal-weight patients, but this was not statistically significant (P=0.11; two-tailed). The mean value of V (8.4 l) in the normal-weight patients was similar to that reported in the literature. The mean difference in values of CL (18% larger in obese patients) was not clinically or statistically significant. A poor correlation was seen between V and lean body weight (r 2=0.05). There was a moderate correlation between V and total body weight (r 2=0.52) and between V and adjusted body weight (r 2=0.55); adjusted body weight=[lean body weight + 0.4(total body weight – lean body weight)]. Total body weight and adjusted body weight provided a better correlation with CL (r 2=0.39, 0.32, respectively) than did lean body weight (r 2=0.01). Conclusion: These results suggest that doses of dalteparin in obese patients should be based on total body weight or an adjusted body weight, but not lean body weight. This study highlights some potential differences in the pharmacokinetics of dalteparin in individuals who are obese, and further work is necessary to quantify these differences in more detail.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280000141
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  • 2
    Electronic Resource
    Electronic Resource
    Cyclic AMP regulates basement membrane heparan sulfate proteoglycan, perlecan, metabolism in rat glomerular epithelial cells (1996)
    Springer
    Molecular and cellular biochemistry 162 (1996), S. 65-73 
    Details
    ISSN: 1573-4919
    Keywords: cAMP ; prostaglandins ; glomerular basement membrane ; perlecan ; glomerular epithelial cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Perlecan, the basement membrane heparan sulfate proteoglycan (HSPG), has been fully cloned from mouse and human tissues. When a cRNA probe of murine perlecan cDNA was employed in RNase protection assay to test whether rat glomerular epithelial cells (GEC) constitutively express perlecan, several bands of hybridization were seen, suggesting that sequences between rat and murine perlecan may not be identical. Using primers based on published cDNA sequences of murine and human perlecan and polyA+ RNA of rat GEC, we synthesized a 497 by product (RPD-1) by RT PCR. The deduced aminoacid sequence showed an 85% and 88% homology with domain I of murine and human perlecan, respectively. The three putative sites containing the consensus sequence SGD for attachment of heparan sulfate chains were fully conserved in the rat perlecan as was a site (NFT) for attachment of N-linked oligosaccharide. RPD-I detected a 〉 9.5 kb transcript of perlecan in RNA of GEC, similar in size to that present in rat glomeruli. Employing a riboprobe synthesized from RPD-I in RNase protection assay we examined whether dbcAMP regulated perlecan expression in the GEC. At 1, 6, 24 and 48 h of incubation, l mM dbcAMP caused 43%, 32%, 47% and 40% reduction in mRNA abundance of perlecan, respectively. Immunoprecipitation showed a corresponding reduction of 61%, 70% and 65% in the synthesis of 35SO4 labeled basement membrane HSPG by the GEC following 12, 24 and 48 h of incubation with dbcAMP Following incubation for 1 and 24 h prostaglandins, PGE1 and PGE2 (1 uM), known activators of glomerular adenylate cyclase, reduced perlecan mRNA abundance to a similar extent as dbcAMP on northern analysis. Our results show that glomerular basement membrane HSPG synthesized by the GEC belongs to the perlecan family. Decrease of GEC perlecan gene expression and synthesis by cAMP and prostaglandins may be of relevance to proteinuric states characterized by activation of these mediators.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00250997
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    Paper (German National Licenses)
    Fulltext
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