Correlations between dose, plasma concentrations, and antispastic action of tizanidine (Sirdalud)

Abstract

In a double blind, placebo controlled, cross over study the correlations between single doses (2, 4, and 8 mg), plasma concentrations, and antispastic action of tizanidine were investigated in 16 patients with extensor spasticity of the legs due to multiple sclerosis. An electrogoniometer was used to assess muscle tone at knee extensors, applying Wartenberg's pendulum test. Blood samples, a clinical assessment of muscle tone by the Ashworth scale, and muscle strength by the British Medical Research Council scale were obtained concomitantly. Confirmatory analysis using the change in the relaxation index (R2 value) 1.5 hours after each treatment, showed a statistically significant (p = 0.0123) linear dose-response relation between single doses and antispastic action of tizanidine. Further statistical analysis showed a strong within patient linear correlation between plasma concentrations and antispastic action at 4 and 8 mg doses (p = 0.014 and 0.004 respectively), but only weak between patient correlations. The analysis of the dose-plasma concentration relation showed results consistent with linear pharmacokinetics. The comparison of changes in the R2 ratio with concomitant Ashworth scores showed a significant correlation between the two. It is concluded that there are linear correlations between single doses, plasma concentrations, and antispastic action of tizanidine. Because of the strong within patient but weak between patient correlation between plasma concentrations and antispastic action of tizanidine the effective doses should be determined individually.