Search our Test Catalog. Specify what to search (name, test code, titles, everywhere) and how to search (begins with, contains)

Unit Code 81255:
Baclofen, Serum

Print Friendly View
Print Page Email Page

Useful For

Confirming suspected baclofen toxicity in patients presenting in a

confused or obtunded state, although routine monitoring of all

patients taking baclofen is not indicated. Several studies in recent

years have shown that patients not responding well to baclofen

given orally do respond to baclofen given intrathecally by infusion

with an implantable, programmable pump.  It has not yet been

demonstrated that monitoring of baclofen, either in serum or CSF,

contributes to the management of these patients.  

Clinical Information

Baclofen (Lioresal) is a muscle relaxant used to treat muscle

rigidity and spastic paresis in patients with multiple sclerosis

or spinal cord injury. 

 

Baclofen was designed as an analog of gamma-aminobutyric acid

(GABA). Although its mechanism of action has not been completely

elucidated, presumably it functions by interacting with GABA-B

receptors. At low doses, baclofen reduces Ca influx in presynaptic

afferent sensory neurons in the ventral horn, thereby inhibiting

release of excitatory neurotransmitters such as aspartate and

glutamate. At higher doses, baclofen hyperpolarizes the post-synaptic

motorneuron by enhancing K conductance.  The net effect is a

reduction in the frequency and severity of flexor and extensor

spasms as well as reduction in flexor tone.

 

Bioavailability is essentially 100% after oral administration.

Baclofen circulates 30% bound to plasma proteins and has an

elimination half-life that varies between 2 and 6 hours. Because

of the short half-life, the drug is usually dosed 3 or 4 times per day.

The recommended maximum daily dose is 80 mg, although higher

doses are required in some patients.  Hepatic metabolism is minimal;

elimination occurs predominantly by renal mechanisms, with 85% of the

parent drug excreted unchanged in urine. Baclofen clearance is identical

to creatinine clearance in most patients.  Volume of distribution has been

reported as 0.9 - 2.4 L/kg.

 

The most common side effect is drowsiness.  Other adverse effects

include insomnia, dizziness, weakness, diplopia, ataxia, palpitations,

and mental confusion. Because of the high prevalence of depression

among patients taking baclofen, overdoses are not uncommon. Respiratory

depression, seizures, and coma may occur; several fatalities attributable

to baclofen alone have been documented. In patients with compromised

renal function, toxic concentrations can also develop on standard doses.

 

Baclofen was designed to be more hydrophobic than GABA to facilitate

penetration of the blood-brain barrier in patients receiving oral

doses.  Although penetration does occur, serum concentrations exceed

cerebrospinal fluid (CSF) concentrations by 1-2 orders of magnitude. 

However, serum concentration does provide an index of CSF concentration,

because there is a rough proportionality between serum and CSF concentrations

at steady-state.

 

Typical of many drugs, the relationship between administered dose

and steady-state serum concentration shows considerable interindivi-

dual variability. Moreover, patients with spinal cord injury may

have an altered volume of distribution secondary to loss of muscle

mass, which can enhance such variability.

Reference Values

Therapeutic concentration:  80-400 ng/mL

Toxic concentration:  >1,000 ng/mL

Interpretation

Patients receiving normal daily doses, typically 40-80 mg/day,

usually show a positive therapeutic response at a serum concentration

between 80-400 ng/mL in a specimen drawn 4 hours after the last

oral dose. Therapeutic efficacy decreases when the serum concen-

tration decreases below 80 ng/mL.

 

Toxic symptoms are usually observed when serum concentrations

exceed 1,000 ng/mL; in fatal cases, concentrations have exceeded

10,000 ng/mL.

Cautions

More than 60 different drugs were tested for possible interference

in the assay. Salicylic acid (an aspirin metabolite) has the potential

to interfere; the patient should not have taken aspirin within 24 hours of

specimen collection.

 

Other possible interfering drugs include gentamicin, penicillin,

and lidocaine.

Clinical Reference

1.   Cedarbaum JM, Schleifer LS:  Drugs for Parkinson's disease,

      spasticity, and acute muscle spasms.  In The Pharmacological Basis

      of Therapeutics.  Edited by AG Gilman, TW Rall, AS Nies, P Taylor.

      8th edition. New York, Pergamon Press, 1990, pp 479-480

 

2.   Faigle JW, Keberle H:  The chemistry and kinetics of Lioresal.

      Postgrad Med J 1972;48:9-13

 

3.   Fraser AD, MacNeil W, Isner AF:  Toxicological analysis of a fatal

      baclofen (Lioresal) ingestion.  J Forensic Sci 1991;36:1596-1602

Key