Simple approach to predict the maximal effect elicited by a drug when plasma concentrations are not available or are dissociated from the effect, as illustrated with chondroitin sulfate data.

analysis of the relationship between the pharma-cologic response of a drug and its dose or its plasma concentrations is essential to determine the adequate dosage to use, to evaluate the benefits and the risks of dosage adjustment, to compare its potency with that of other drugs, and to predict the repercussions on the effect of drug-drug interactions. The analysis of the changes of the response as a function of the plasma concentrations of a drug allows prediction of the maximal effect (E max) elicited by the drug and the concentration eliciting 50% of E max (EC 50). Estimation of E max and EC 50 with the E max model 1 is simple whenever the relationship between response and plasma concentrations is direct (ie, the relationship depicts a hyperbola). The E max model does not allow analysis of the effect-concentration relationship of every single drug, since there are drugs that are not absorbed such as cholestyra-mine and colestipol, drugs generating low to undetectable plasma concentrations such as alendronate, drugs rapidly degraded to compounds with lower molecular weight, such as hyaluronic acid, chondroitin sul-fate, and glucosamine, drugs originating many active metabolites such as antipsychotic agents, and drugs eliciting an effect that is measurable after a long period of exposure, such as hormones, antidepressants, alen-dronate, chondroitin sulfate, and the like. Under all these circumstances, the analysis of the effect-concentration relationship with the E max model may be difficult or impossible. Furthermore, for the venue of gene therapy, with the use of recombinant proteins and other natural products, the method to assay the plasma concentrations of the active compound may be less accessible and make more difficult the calculation of E max and EC 50. This study aimed to put forward a simple approach to assess E max when the plasma concentrations of the active moiety are not available, when the kinetics and the time course of the dynamics are dissociated, when multiple active compounds are present, when several drugs are used to reach the same goal, when there is a cumulative effect as a function of time, and when an effect is to be assessed in the absence of drug therapy. The proposed method is not a substitute for the E max method but may be an alternative approach in situations where the E max method cannot be applied. The approach proposed to estimate E max was validated by analyzing the pharmacologic response …