Pharmacodynamics of chlorzoxazone in rats

Pharmacological effect-time profiles of a centrally acting muscle relaxant, chlorzoxazone, were evaluated by both rotarod and crossed extensor reflex (CER) methods. Drug response was measured by percent change in the remaining time on the rod for the former method and in intensity of isometric contraction of the muscle for the latter method. The drug response was quantitated using the logarithmic-logistic function and then biophase levels were calculated. The results indicated that the maximum response was observed 10 min after drug administration for both methods at every dose studied. However, the values of ED50 indicated that the CER method was more sensitive than the other. Pharmacodynamic analysis offered the results that the dose-normalized biophase levels for each dose obtained from the CER method were coincident with each other and that the logarithmic-logistic function was proven to be of use for the pharmacodynamic modeling which could simply assess the bioavailability. On the other hand, all dose-normalized values obtained from the rotarod method did not scatter around the same line. This evidence indicated a violation of assumption for the pharmacodynamic analysis. From the above data, the CER method proved to be of use for assessing the drug response based on the dose-independent kinetics with high sensitivity.