A controlled pharmacokinetic evaluation of tizanidine and baclofen at steady state.

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Shellenberger MK, Groves L, Shah J, Novack GD

A controlled pharmacokinetic evaluation of tizanidine and baclofen at steady state.

Drug Metab Dispos. 1999 Feb;27(2):201-4.

PubMed ID

9929503 [ View in PubMed

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Abstract

Clinical trials with tizanidine when administered alone have shown that 5-chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiodiazole (tizanidine) is safe and effective for spasticity control. However, given its mechanism of action and requirement for titration, clinical experience suggests that tizanidine is likely to be used in combination with other antispastic agents with different mechanisms of action, such as baclofen. The objective of this study was to examine the pharmacokinetics of both tizanidine and baclofen under steady-state conditions when administered alone or concomitantly. This was a randomized, three-period, multiple-dose, Latin Square design study consisting of tizanidine HCl, 4 mg t.i.d. for seven consecutive doses; baclofen, 10 mg t.i.d. for seven consecutive doses; and both regimens simultaneously for seven consecutive doses. Drug administration was performed every 8 h, three times daily. Fifteen normal men served as study subjects. A priori, a clinically significant difference was set as 30%. Concentrations of tizanidine and baclofen were nearly identical during the single and concomitant dosing periods. All of the calculated steady-state pharmacokinetic parameter changes for baclofen, tizanidine, and its major metabolites were within the 30% criterion. Small differences in renal clearance were observed when the two drugs were coadministered, but these changes are unlikely to be clinically important. Thus, it is unlikely that coadministration of tizanidine and baclofen during dose-titration of the former will result in a pharmacokinetic interaction.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Tizanidine	Cytochrome P450 1A2	Protein	Humans	Unknown	Substrate	Details