Source: Υπουργείο Υγείας (CY) Revision Year: 2021 Publisher: Remedica Ltd, Aharnon Str., Limassol Industrial Estate, 3056 Limassol, Cyprus
Pharmacotherapeutic group: Muscle relaxants; Muscle relaxants, centrally acting agents
ATC code: M03BX01
Baclofen is an antispastic agent acting at the spinal level. A gamma-aminobutyric acid (GABA) derivative, Baclofen is chemically unrelated to other antispastic agents.
Baclofen depresses monosynaptic and polysynaptic reflex transmission, probably by stimulating the GABAB-receptors, this stimulation in turn inhibiting the release of the excitatory amino acids glutamate and aspartate. Neuromuscular transmission is unaffected by Baclofen.
The major benefits of Baclofen stem from its ability to reduce painful flexor spasms and spontaneous clonus thereby facilitating the mobility of the patient, increasing his independence and helping rehabilitation
Baclofen also exerts an antinociceptive effect. General well being is often improved and sedation is less often a problem than with centrally acting drugs.
Baclofen stimulates gastric acid secretion.
Baclofen is rapidly and completely absorbed from the gastrointestinal tract. Following oral administration of single doses (10-30 mg) peak plasma concentrations are recorded after 0,5 to 1,5 hours and areas under the serum concentration curves are proportional to the dose.
The volume of distribution of baclofen is 0.7 l/kg. The protein binding rate is approximately 30% and is constant in the concentration range of 10 nanogram/mL to 300 microgram/mL. In cerebrospinal fluid active substance concentrations are approximately 8.5 times lower than in the plasma.
Baclofen is metabolised to only a minor extent. Deamination yields the main metabolite, β-(p-chlorophenyl)-4-hydroxobutyric acid, which is pharmacologically inactive.
The plasma elimination half-life of baclofen averages 3 to 4 hours.
Baclofen is eliminated largely in unchanged form. Within 72 hours, approximately 75% of the dose is excreted via the kidneys with about 5% of this amount as metabolites.
The pharmacokinetics of baclofen in elderly patients are virtually the same as in patients below 65 years of age. Following a single oral dose, elderly patients have slower elimination but a similar systemic exposure of baclofen compared to adults below 65 years of age. Extrapolation of these results to multi-dose treatment suggests no significant pharmacokinetic difference between patients below 65 years of age and elderly patients.
Following oral administration of 2.5 mg Baclofen tablet in children (aged 2 to12 years), Cmax of 62.8±28.7 nanogram/mL, and Tmax in the range of 0.95-2 h have been reported. Mean plasma clearance (Cl) of 315.9 mL/h/kg; volume of distribution (Vd) of 2.58 L/kg; and half-life (T1⁄2) of 5.10 h have been reported.
No pharmacokinetic data are available in patients with hepatic impairment after administration of baclofen. However, as the liver does not play a significant role in the disposition of baclofen, it is unlikely that baclofen pharmacokinetics would be altered to a clinically significant level in patients with hepatic impairment.
No controlled clinical pharmacokinetic study is available in patients with renal impairment after administration of baclofen. Baclofen is predominantly eliminated unchanged in urine. Sparse plasma concentration data collected only in female patients under chronic hemodialysis or compensated renal failure indicate significantly decreased clearance and increased half-life of baclofen in these patients. Dosage adjustment of baclofen based on its systemic levels should be considered in renal impairment patients, and prompt hemodialysis is an effective means of reversing excess baclofen in systemic circulation.
Baclofen increases the incidence of omphaloceles (ventral hernias) in the foetuses of rats given approximately 13 times the maximum oral dose (on a mg/kg basis) recommended for human use. This was not seen in mice or rabbits.
An apparently dose related increase in the incidence of ovarian cysts, and a less marked increase in enlarged and/or haemorrhagic adrenals have been observed in female rats treated for 2 years. The clinical relevance of these findings is not known.
Experimental evidence to date suggests that baclofen does not possess either carcinogenic or mutagenic properties.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
