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  • 1
    Electronic Resource
    Electronic Resource
    Clinical applicability of current pharmacokinetic models: Splanchnic elimination of 5-fluorouracil in cancer patients (1988)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 16 (1988), S. 229-249 
    Details
    ISSN: 1573-8744
    Keywords: Michaelis-Menten kinetics ; sinusoidal perfusion model ; venous equilibration model ; distributed model ; convection-dispersion model ; organ heterogeneity ; bioavailability ; pooling of data ; kinetic parameter estimation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract What can be inferred from limited clinical data by using current models of hepatic elimination? We examined this question by analyzing previously published data on the steady-state uptake of the anticancer agent 5-fluorouracil (5-FU) in seven cancer patients in terms of the venous equilibration model, the undistributed and distributed forms of the sinusoidal perfusion model, and the convection-dispersion model. Because of appreciable extrasplanchnic removal of 5-FU, the value of the steady infusion rate was not used in our analysis. When the data from all patients were pooled by plotting the measured hepatic venous concentration against the measured hepatic arterial concentration, the high concentration data fell on a limiting straight line of slope 1, indicating that at high dose rates elimination of 5-FU in both the liver and gastrointestinal tract was close to saturation. The intercept of this line gave a model-independent estimate of Vmax/Q= 48.0±11.6 (SD) μM for the pooled data set, where Vmax is the maximum splanchnic elimination rate of 5-FU, and Q is the hepatic blood flow. The low concentration data points fell on a limiting straight line through the origin, from which model-dependent values of the Michaelis constant were determined. The venous equilibration model gave K m=9.4μM,while the undistributed sinusoidal perfusion model gave K m * =26,5μM. With these values of K m,both models fit the pooled data equally well. These methods were applied to analyses of the five individual data sets which contained sufficiently high concentration data points. The resulting mean values were Vmax/Q=41.0±5.1 (sem) μM,K m=8.4±1.3μM and K m * =23.2±3.2 μM. However, the splanchnic region is a highly heterogeneous organ system, for which an undistributed analysis provides no more than an upper bound on the Michaelis constant K m + (K m + ⩽K m * ).A perfusion model distributed to represent total splanchnic elimination is developed in the Appendix. Using previous estimates of the degree of functional heterogeneity in the liver alone, this model yields K m + values for individual patients which have a mean of 20.3±2.8 μM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062135
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Response of the european elm bark beetle,Scolytus multistriatus, to host bacterial isolates (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 1133-1149 
    Details
    ISSN: 1573-1561
    Keywords: Smaller European elm bark beetle ; Scolytus multistriatus ; Coleoptera ; Scolytidae ; elm bacterial isolates ; gamma irradiation ; trapping
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The response of the European elm bark beetle,Scolytus multistriatus, to host bacterial isolates was studied qualitatively under field conditions. Initial experiments indicated that such isolates were attractive to in-flight beetles. These isolates, identified asBacillus subtilis (five strains),B. pumilus, andEnterobacter cloacae, were grown on nutrient agar in glass vials and attached to sticky traps in elm woods. Although beetles were caught on the bacterial isolate-baited traps, the catches were variable, inconsistent, and often contradictory from one experiment to another. High numbers ofS. multistriatus were caught on traps baited with three strains ofB. subtilis, but in addition to thesubtilis strains, there were also aerial contaminants in the treatments, namelyE. aerogenes, Corynebacterium sp., andFlavobacterium sp. Also, relatively high catches were recorded on nutrient agar controls. When elm wood-bark plugs, sterilized (by gamma irradiation) and unsterilized, were placed in vials with the host bacterial isolates, the presence or absence of fresh elm, gamma irradiated or not, had no noticeable effect on beetle attractancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00987519
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    Paper (German National Licenses)
    Fulltext
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