A pharmacokinetic-pharmacodynamic model for intrathecal baclofen in patients with severe spasticity

作者：Heetla H W^*; Proost J H; Molmans B H; Staal M J; van Laar T

来源：British Journal of Clinical Pharmacology, 2016, 81(1): 101-112.

DOI：10.1111/bcp.12781

• baclofen
• injections
• spinal
• pharmacokinetics
• pharmacology

AimsIntrathecal baclofen (ITB) has proven to be an effective and safe treatment for severe spasticity. However, although ITB is used extensively, clinical decisions are based on very scarce pharmacokinetic-pharmacodynamic (PKPD) data. The aim of this study was to measure baclofen CSF concentrations and clinical effects after administration of various ITB boluses in patients with spasticity and to create a PKPD model for ITB.
MethodsTwelve patients with severe spasticity received four different bolus doses of ITB (0, 25, 50, 75g and an optional dose of 100g), administered via a catheter with the tip at thoracic level (Th) 10. After each bolus, 10 CSF samples were taken at fixed time intervals, using a catheter with the tip located at Th12. Clinical effect was assessed by measuring spasticity with the Modified Ashworth Scale (MAS). These data were used to develop a PKPD model.
ResultsAll patients achieved an adequate spasmolytic effect with ITB doses varying from 50 to 100g. No serious side effects were observed. CSF baclofen concentrations, as well as the clinical effects, correlated significantly with ITB doses. The PK model predicted a steep spinal concentration gradient of ITB along the spinal axis. The clinical effect could be predicted using a delayed-effect model.
ConclusionsITB is an effective and safe therapy with, however, a steep concentration gradient along the spinal axis. This means that the administered baclofen is staying mainly around the catheter tip, which stresses the importance to position the ITB catheter tip closely to the targeted spinal level.

• 出版日期2016-1