Plasma and cerebrospinal fluid levels of baclofen (lioresal ®) at optimal therapeutic responses in spastic paresis

Abstract

Eleven patients with spastic paresis and marked muscular hypertonus were treated with the GABA derivative, baclofen (Lioresal ®), given in 3 oral daily does (30–90 mg per day). After a period of unchanged medication (3 days-1 year) at doses yielding an optimal therapeutic response, determinations were made of the concentrations of unchanged baclofen in plasma and CSF at predetermined intervals after medication. The plasma and CSF levels were compared to the therapeutic responses in patients with α- and γ-spasticity, the type of spasticity being differentiated with cryotests. The concentrations of the drug in plasma showed levels and half-lives corresponding to those observed after the administration of single oral doses to healthy volunteers. Thus, there were no findings indicating an accumulation of the drug in plasma during long-term medication. Confirming previous studies 7 patients with γ-spasticity responded well to the therapy, whereas deterioration or lack of functional improvement was seen in 3 out of 4 patients with α-spasticity. Optimal therapeutic responses in patients with γ-spasticity were obtained at very different levels of the drug in plasma and CSF. In patients with α-spasticity in whom no antispastic effects were observed, the levels of baclofen in plasma and CSF were within the same range as in several functionally improved patients with γ-spasticity. The results are in accordance with the concept that the type of spasticity is crucial in reaching an improvement from baclofen treatment in patients with spastic pareses.