title: A pilot study assessing pharmacokinetics and tolerability of oral and intravenous baclofen in healthy adult volunteers.
abstract: Our objective was to characterize baclofen pharmacokinetics and safety given orally and intravenously. Twelve healthy subjects were enrolled in a randomized, open-label, crossover study and received single doses of baclofen: 3 or 5 mg given intravenously and 5 or 10 mg taken orally with a 48-hour washout. Blood samples for baclofen analysis were collected pre-dose and at regular intervals up to 24 hours post-dose. Clinical response was assessed by sedation scores, ataxia, and nystagmus. Mean absolute bioavailability of oral baclofen was 74%. Dose-adjusted areas under the curve between the oral and intravenous arms were statistically different (P = .0024), whereas area under the curve variability was similar (coefficient of variation: 18%-24%). Adverse effects were mild in severity and not related to either dose or route of administration. Three- and 5-mg intravenous doses of baclofen were well tolerated. Seventy-four percent oral bioavailability indicates that smaller doses of intravenous baclofen are needed to attain comparable total drug exposures.
authors.affiliation: Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA agar0152@umn.edu.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Agarwal
authors.affiliation: Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Kriel
authors.affiliation: Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Cloyd
authors.affiliation: Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Coles
authors.affiliation: Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Scherkenbach
authors.affiliation: Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Tobin
authors.affiliation: Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Linda E
authors.initials: LE
authors.lastname: Krach
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001418:Baclofen / Q000097:blood* / Q000493:pharmacokinetics*; D001682:Biological Availability; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004562:Electrocardiography; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D009125:Muscle Relaxants, Central / Q000097:blood* / Q000493:pharmacokinetics*; D010865:Pilot Projects; D013997:Time Factors
chemical_list: D009125:Muscle Relaxants, Central; D001418:Baclofen
keywords: baclofen; baclofen withdrawal; intravenous therapy; muscle spasticity; pharmacokinetics