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  • 1
    Electronic Resource
    Electronic Resource
    Difference of train-of-four fade induced by nondepolarizing neuromuscular blocking drugs: a theoretical consideration on the underlying mechanisms (1995)
    Springer
    Journal of anesthesia 9 (1995), S. 333-337 
    Details
    ISSN: 1438-8359
    Keywords: Train-of-four fade ; Nondepolarizing neuromuscular blocking drugs ; Acetylcholine ; Mobilization ; Model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nondepolarizing neuromuscular blocking drugs induce train-of-four (TOF) fade, i.e., the reduction of the fourth to the first twitch height in a train under TOF stimulation. It has been observed that the degree of TOF fade varies with the drug used and is inversely correlated with the potencies of the drug. In this study, the cause of difference of TOF fade was considered using a dynamic model. The model was based on the following assumptions: (1) Twitch response is evoked by the binding of acetylcholine (ACh) molecules to the postsynaptic nicotinic receptors in a neuromuscular junction, (2) time-dependent ACh mobilization in a motor nerve terminal results in less ACh output at the fourth stimulus in a train than at the first stimulus, (3) the drugs compete with ACh for the postsynaptic receptors and inhibit the receptor-binding of ACh, and (4) the drugs have various affinities for the receptors. This study suggested that the difference of affinities of the drugs for postsynaptic ACh receptors may cause the difference of TOF fade.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02479947
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  • 2
    Electronic Resource
    Electronic Resource
    Kinetics of d-tubocurarine disposition and pharmacologic response in rats (1983)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 47-61 
    Details
    ISSN: 1573-8744
    Keywords: d-tubocurarine ; pharmacokinetics ; pharmacodynamics ; multicompartrnent model ; Hill equation ; plasma ; tibialis anterior muscle ; protein binding ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract After bolus intravenous dosing of d-tubocurarine (d-TC) to rats, the twitch heights of the tibialis anterior muscle indirectly stimulated were followed, and its decrease was defined as pharmacologic response of d-TC. The relation between dose and response intensity was found to be well described with Hill's equation. According to a theory proposed by Smolen, Hill's equation was also applicable to the biophase d-TC concentration-response relation; the time courses of the relative biophase d-TC concentration indicated linear kinetics with dose levels ≤0.15 mg/kg and the occurrence of dose-dependent disposition with 0.30 mg/kg. After bolus i.v. dosing of3H-d-TC, plasma d-TC concentration obeyed a dose-independent two compartment model with doses ≤0.15mg/kg, but not with 0.30 mg/kg. This finding matched the above estimated with pharmacologic data. The active metabolite was not found in plasma and urine. The extent of d-TC plasma protein binding was independent of the wide range of plasma levels and its mean (±SD) value was 30.5 (±3.8). Plasma d-TC levels and pharmacologie response intensity were well correlated by Hill's equation and a three compartment model (the general two and the biophase compartments) in the dose range ≤0.15 mg/kg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061767
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Kinetics of combined drug action (1993)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 21 (1993), S. 593-607 
    Details
    ISSN: 1573-8744
    Keywords: Combined drug action ; Hili equation ; isobologram ; concentration-effect ; correlation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract For the purpose of obtaining quantitative concentration-effect relationship for combined drugs, rationales of the Hill equation were inferred and five models, i.e., normal distribution (NRD), derivative of R (DRV), vacancy-dependent binding (VDB), equiresponse (EQR), and independence (IND), were proposed to estimate the intensity of the combined drug action. In conclusion, we could not come up to the unique concentration-effect relationship. Among the five models, the EQR, NRD, and VDB models gave almost identical response intensity. Discrimination of these three models is not of great importance. The DRV model gave a characteristic concave isobologram (overadditive), for a given ratio of Hill constants and independent of pharmacologic effect. In contrast, the IND model was able to cope with convex isobolograms (underadditive).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059116
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and Pharmacodynamic Evaluation for Tissue-Selective Inhibition of Cholesterol Synthesis by Pravastatin (1998)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 26 (1998), S. 329-347 
    Details
    ISSN: 1573-8744
    Keywords: HMG-CoA reductase inhibitors ; pravastatin ; tissue-selectivity ; cholesterol synthesis ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The tissue-selective inhibition of cholesterol synthesis by pravastatin was evaluated pharmacokinetically and pharmacodynamically. Plasma, tissue, urine, and bile concentrations were measured after iv bolus injection of pravastatin to rats at various doses. The total body clearance and steady state volume of distribution decreased with increasing dose. A saturable biliary excretion was also observed. The time course of plasma and liver concentrations was described by a three-compartment model, consisting of a central compartment, a deep compartment with an nonsaturable uptake process, and a shallow compartment with saturable uptake and nonsaturable elimination processes. It suggests that a mechanism for the decrease in the total body clearance and distribution volume might be explained by a saturation of pravastatin uptake into the liver. Plasma concentration data after oral administration was also fitted to the same model by connecting an absorption compartment to the shallow compartment. The inhibitory activity of pravastatin against cholesterol synthesis in liver could be related to the concentration in the shallow compartment via a sigmoidal Emax model and the obtained pharmacodynamic parameters were comparable to those in vitro. Results suggest that the carrier-mediated hepatic uptake of pravastatin is actually responsible for the hepatoselective inhibition of cholesterol synthesis under physiological conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1023237510458
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  • 5
    Electronic Resource
    Electronic Resource
    Kinetics of Swelling of Compressed Cellulose Matrices: A Mathematical Model (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 329-333 
    Details
    ISSN: 1573-904X
    Keywords: swelling ; compressed matrix ; diffusion ; methyl cellulose ; hydroxypropyl cellulose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. A model for swelling time course of compressed cellulose matrix is presented. Methods. The model incorporates the two most important features: water penetration by diffusion and volume change due to swelling. Approximations of the model for small t values and for large t values are also derived, which are utilized in a handy routine for estimation of swelling parameters. Results. The observed time courses of thickness change with compressed matrices of methyl cellulose and hydroxypropyl cellulose agree well with the calculated values of the proposed model. Conclusions. The proposed model is compatible with the observed swelling kinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016071921358
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    Paper (German National Licenses)
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