The Kinetics of Effect of Neuromuscular Blocking Drugs.
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概要
- 論文の詳細を見る
In attempts to derive pharmacokinetic constants from effect data three methods were explored, using non-depolarizing neuromuscular blocking drugs as the paradigm for obtaining effect data. The first method, based on the simple assumption that following two doses, the drug concentrations at times of equal effect during recovery, were equal. Provided that recovery took place in the log-linear drug elimination phase, the elimination rate constant (β) could be calculated. This method proved rather inaccurate, a second method, again dependent on recovery in the log-linear phase yielded a constant which was the product of f and the exponent of the Hill equation (s). This method yielded results within 20% of values calculated from plasma drug assays, and it was demonstrated that the time-effect curve could be described from knowledge of this constant. The third method, using non-linear curve fitting technique, derived values for the rate constants of plsma redistribution (α) and elimination (β) as well as for the rate constant of elimination from an effect compartment (keo). If the values were derived from the effect of two doses of a drug, the intensity and duration of effect of a third dose could be predicted with reasonable accuracy. The dose dependent constants of the usual compartmental equations for the plasma concentration of a drug (A and B) could be derived in terms of the EC50. The method can be applied to any drug whose effect can be measured and whose maximal effect can be defined. We believe that the method may be useful in rapidly and inexpensively estimating population kinetic parameters, and in screening drugs.
- The Keio Journal of Medicineの論文
著者
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Graham Garry
School of Physiology and Pharmacology, University of New South Wales
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Torda Thomas
Department of Anaesthesia and Intensive Care, Prince Henry and Prince of Wales Hospital
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Warwick Neil
Department of Anaesthesia and Intensive Care, Prince Henry and Prince of Westmead Hospital