title: Pharmacokinetic characterization of baclofen in patients with chronic kidney disease: dose adjustment recommendations.
abstract: The pharmacokinetics of baclofen is well delineated in subjects with normal kidney function (KF); however, pharmacokinetics data in patients with chronic kidney disease (CKD) are not and dosage recommendations remain empirical. The effects of CKD on baclofen pharmacokinetics were assessed through a multi-center, open-label, single 5-mg dose, pharmacokinetics study. The KF was measured as the creatinine clearance (CrCL) calculated with the Cockroft-Gault (C-G) equation or as the estimated glomerular filtration rate (eGFR) using subjects' CKD-EPI equation. Subjects were assigned to 1 of 4 groups based on their CrCL (>80 mL/min, 50-80 mL/min; 30-50 mL/min and <30 mL/min). Cmax was not statistically different between the groups, while AUC and T1/2el increased, and CL/F decreased, with increasing severity of CKD. Baclofen's oral clearance and CrCL were statistically significantly correlated, and the trend was the same when classifying subjects either with the CKD-EPI or C-G equations. Linear equations using KF as variable were set to recommend individual dose reduction in CKD patients. Results suggest a mean dose reduction of 1/3, 1/2, and 2/3 in patients with mild, moderate, and severe CKD respectively, in order to achieve baclofen exposure comparable to that observed in healthy subjects.
authors.affiliation: Division of Clinical Pharmacology, inVentiv Health Clinical, Montreal, Quebec, Canada.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Vlavonou
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.|Department of Pharmacy, McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Marc M
authors.initials: MM
authors.lastname: Perreault
authors.affiliation: Division of Clinical Pharmacology, inVentiv Health Clinical, Montreal, Quebec, Canada.
authors.forename: Olivier
authors.initials: O
authors.lastname: Barrière
authors.affiliation: Division of Clinical Pharmacology, inVentiv Health Clinical, Quebec, Quebec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Shink
authors.affiliation: Division of Clinical Pharmacology, inVentiv Health Clinical, Quebec, Quebec, Canada.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Tremblay
authors.affiliation: Clinical division, inVentiv Health Clinical, Montreal, Quebec, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Larouche
authors.affiliation: Centre de recherche Hôpital Maisonneuve-Rosemont, Montréal, Canada.|Département de Médecine et de Pharmacologie, Université de Montréal, Montréal, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pichette
authors.affiliation: Division of Clinical Pharmacology, inVentiv Health Clinical, Montreal, Quebec, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Tanguay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001418:Baclofen / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D058786:GABA-B Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*
chemical_list: D058786:GABA-B Receptor Agonists; D009125:Muscle Relaxants, Central; D003404:Creatinine; D001418:Baclofen
keywords: baclofen; dose adjustment recommendations; kidney disease; pharmacokinetics; renal impairment; safety