Plasma and urinary excretion kinetics of oral baclofen in healthy subjects
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Baclofen, a centrally acting muscle relaxant, is used in the treatment of spasticity. Its pharmacokinetics has been derived from plasma and urine data in four healthy subjects, whose renal function was simultaneously measured.
After oral administration of a single 40 mg dose, baclofen was mainly excreted unchanged by the kidney, 69 (14) %. The half-life, calculated from extended least squares modelling (ELSMOS) both of plasma and urine data was 6.80 (0.68) h, which is longer than reported in most studies based solely on plasma data.
The renal excretion rate constant had the high mean value of 0.35 (0.24) h−1, and the apparent renal clearance of baclofen equalled the creatinine clearance. Passive tubular reabsorption is relatively unimportant, since no dependence was observed on variables urine flow or pH.
Although active tubular secretion may contribute to its renal clearance, as shown by the effect of coadministration of probenecid, glomerular filtration appears to be the dominant transport mechanism.
Key wordsbaclofen renal function healthy subjects pharmacokinetics probenecid tubular secretion
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- 1.Young RR, Delwaide PJ (1981) Spasticity. N Engl J Med 304: 96–99Google Scholar
- 2.Faigle JW, Keberle H (1972) The chemistry and kinetics of lioresal. Postgrad Med J [Suppl]: 9–13Google Scholar
- 3.Kochak GM, Rakhit A, Wagner WE, Honc F, Waldes L, Kershaw RA (1985) The pharmacokinetics of baclofen derived from intestinal infusion. Clin Pharmacol Ther 38: 251–257Google Scholar
- 4.Wuis EW, Dirks MJM, Termond EFS, Vree TB, Van der Kleijn E. Comparison of the pharmacokinetics of intravenously administered rac-baclofen and its (−)-(R)-and (+)-(S)-enantiomers in dogs. Clin Pharmacol Res (in press)Google Scholar
- 5.Seyfert S, Kraft D, Wagner K (1981) Baclofen-Dosis bei Haemodialyse und Niereninsuffizienz. Nervenarzt 52: 616–617Google Scholar
- 6.Dahlin PA, George J (1984) Baclofen toxicity associated with declining renal clearance after ibuprofen. Drug Intell Clin Pharm 18: 805–808Google Scholar
- 7.Hormes JT, Benarroch EE, Rodriguez M, Klass DW (1988) Periodic sharp waves in baclofen-induced encephalopathy. Arch Neurol 45: 814–815Google Scholar
- 8.Hulme A, Maclennan WJ, Ritchie RT, John VA, Shotton PA (1985) Baclofen in the elderly stroke patient its side-effects and pharmacokinetics. Eur J Clin Pharmacol 29: 467–469Google Scholar
- 9.Wuis EW, Dirks RJM, Vree TB, Van der Kleijn E (1985) High-performance liquid chromatographic analysis of baclofen in plasma and urine of man after precolumn extraction and derivatization with o-phthaldialdehyde. J Chromatogr 337: 341–350Google Scholar
- 10.Wuis EW, Van Beijsterveldt LEC, Dirks RJM, Vree TB, Van der Kleijn E (1987) Rapid simultaneous determination of baclofen and its γ-hydroxymetabolite in urine by high-performance liquid chromatography with ultraviolet detection. J Chromatogr 420: 212–216Google Scholar
- 11.Hekster YA, Vree TB, Van Dalen R, Baars AM, Damsma JE (1980) Determination and pharmacokinetics of some β-lactam antibiotic drugs. In: Merkus FWHM (ed) The serum concentration of drugs. Excerpta Medica, AmsterdamGoogle Scholar
- 12.Francis RJ (1984) ELSMOS — An extended least squares modelling system in Fortran 77 for mini- or micro-computer implementation. Comp Prog Biomed 18: 43–50Google Scholar
- 13.Faigle JW, Keberle H, Degen PH (1980) Chemistry and pharmacokinetics of baclofen. In: Feldman RG, Young RR, Koella WP (eds) Spasticity: Disordered motor control. Symposia Specialists, Year Book Medical Publishers, Chicago LondonGoogle Scholar
- 14.Spahn H, Krauss D, Mutschler E (1988) Enantiospecific high-performance liquid chromatographic (HPLC) determination of baclofen and its fluoro analogue in biological material. Pharm Res 5: 107–112Google Scholar
- 15.Krauss D, Spahn H, Mutschler E (1988) Quantification of baclofen and its fluoro analogue in plasma and urine after fluorescent derivatisation with benoxaprofen chloride and thinlayer chromatographic separation. Arzneimittelforsch 38: 1533–1536Google Scholar
- 16.Peterson GM, McLean S, Millingen KS (1985) Food does not affect the bioavailability of baclofen. Med J Aust 42: 689–690Google Scholar
- 17.Krauss D (1988) Untersuchungen zur Razemat- und Enantiomerenkinetik von Baclofen und seinen Fluoranalogons [Thesis, Goethe-Universität, Frankfurt am Main, FRG]. Copy Shop, Darmstadt, S 108Google Scholar
- 18.Wetzels JFM, Huysmans FTM, Koene RAP (1988) Creatinine as a marker of glomerular filtration rate. Neth J Med 33: 144–153Google Scholar