ARE PLASMA-CONCENTRATION VALUES NECESSARY FOR PHARMACODYNAMIC MODELING OF MUSCLE-RELAXANTS

Background: The traditional approach to pharmacokinetic/pharmacodynami c modeling of muscle relaxants requires sampling of plasma to determin e drug concentrations. The authors recently proposed that certain phar macodynamic characteristics (IR(50), the steady-state infusion rate to maintain 50% twitch depression; k(eo), the rate constant for equilibr ation between plasma concentration and effect; and gamma, the Hill fac tor describing sigmoidicity of the concentration-effect relation) coul d be estimated without plasma concentration data. Here estimates for I R(50), k(eo), and gamma determined with and without plasma concentrati on data are compared. Methods: Six volunteers were given 15-60 mu g/kg vecuronium on each of two occasions during anesthesia with propofol, Mechanical responses to train-of-four stimulation were measured at the adductor pollicis and at the laryngeal adductors. Various pharmacokin etic models accounting for the presence and potency of vecuronium's 3- desacetyl metabolite and a sigmoid e-max pharmacodynamic model were fi t to the resulting plasma concentration and effect (adductor pollicis and laryngeal adductors) data to determine IR(50) k(eo), and gamma for each effect. One model related dose to effect without plasma concentr ation data. Results: Values for IR(50)(adductor pollicis), IR(50)(lary ngeal adductors), gamma(adductor pollicis), and gamma(laryngeal adduct ors) mere similar when determined with and without plasma concentratio n values. Values for k(eo)(adductor pollicis) and k(eo)(laryngeal addu ctors) were larger when determined without plasma concentration values compared with those determined with these values; however, the ratio of k(eo)(adductor pollicis) to k(eo)(laryngeal adductors) was similar when determined with and without plasma concentration values. Conclusi ons: Certain pharmacodynamic parameters mere estimated accurately in t he absence of plasma concentration values. This suggests limited utili ty for plasma concentration data under conditions similar to those of the present study.