The question concerns a 36-year-old man with a spastic paraparesis. It is planned to treat the pati

Fråga: The question concerns a 36-year-old man with a spastic paraparesis. It is planned to treat the patient with baclofen for his spasticity. However, he also has a decreased kidney function with a glomerular filtration rate of 39 ml/min.

What should the does of baclofen be? In the past, the patient has been treated with baclofen 40 mg/day, during which neither beneficial effects, nor adverse side-effects, were noted.

Sammanfattning: Seventy per cent of a baclofen dose is excreted unchanged by the kidneys, mainly by glomerular filtration. As the patient in this case has a reduced kidney function, it should be taken into account that plasma half-life and steady-state plasma concentrations of baclofen will be increased by a factor two as compared with a patient with normal kidney function. It should be stressed that dosage schedules of baclofen are individualised with beneficial effects weighted against adverse effects. In cases of overdosage, adverse effects such as hypotonia have been observed.

Svar: Renal excretion is an important pathway in the elimination of baclofen from the human body. Oral administration of a single 40 mg dose to healthy volunteers (1) showed that baclofen is mainly excreted unchanged by the kidneys. Glomerular filtration appears to be the dominant mechanism of renal excretion of baclofen, although active tubular secretion may contribute to a minor extent, as was shown by the inhibitory effect on baclofen clearance by the concomitant administration of probenecid (1). On the whole, renal clearance of baclofen closely mimics creatinine clearance.

Assuming that, in this patient, renal clearance of baclofen is reduced to one-third and that nonrenal clearance is not affected, this would mean a reduction in total clearance of about 50 per cent. Therefore plasma half-life, time to reach steady-state and steady-state plasma concentrations of baclofen can be expected to be increased by a factor 2. As a consequence, the dosing rate should in principle be reduced by one-half, if the same levels as those in a patient with normal kidney function are aimed for.

The usual dosage regimen of baclofen is 15 mg/day initially, followed by 30-75 mg/day (2) with a maximum of up to 100 mg/day (3). However, doses up to 200 mg have been given to patients with paraplegia (4). Common side-effects are drowsiness, nausea and in high doses hypotonia (3). Normally, the plasma half-life of baclofen is 3-4 hours, so in this patient it will probably be 6-8 hours. After a change in dosing new steady-state plasma levels can be expected after 5 half-lives. 1 Wuis EW, Dirks MJM, Termond EFS, Vree TB, van der Kleijn E: Plasma and urinary excretion kinetics of oral baclofen in healthy subjects. Eur J Clin Pharmacol 1989; 37: 181-184 2 FASS 1993; page 994 3 Avery, Drug treatment. 1987; 3rd ed: 1114-1115 4 Drugline nr 08992 (year 1991)