CORRELATIONS BETWEEN DOSE, PLASMA-CONCENTRATIONS, AND ANTISPASTIC ACTION OF TIZANIDINE (SIRDALUD(R))

In a double blind, placebo controlled, cross over study the correlatio ns between single doses (2, 4, and 8 mg), plasma concentrations, and a ntispastic action of tizanidine were investigated in 16 patients with extensor spasticity of the legs due to multiple sclerosis. An electrog oniometer was used to assess muscle tone at knee extensors, applying W artenberg's pendulum test. Blood samples, a clinical assessment of mus cle tone by the Ashworth scale, and muscle strength by the British Med ical 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 ac tion of tizanidine. Further statistical analysis showed a strong withi n patient Linear correlation between plasma concentrations and antispa stic action at 4 and 8 mg doses (p = 0.014 and 0.004 respectively), bu t only weak between patient correlations. The analysis of the dose-pla sma concentration relation showed results consistent with linear pharm acokinetics. The comparison of changes in the R2 ratio with concomitan t 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 betw een plasma concentrations and antispastic action of tizanidine the eff ective doses should be determined individually.