title: The pharmacokinetics of methocarbamol and guaifenesin after single intravenous and multiple-dose oral administration of methocarbamol in the horse.
abstract: A simple LC/MSMS method has been developed and fully validated to determine concentrations and characterize the concentration vs. time course of methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred horses. The plasma concentration-time profiles for MCBL after a single intravenous dose of 15 mg/kg of MCBL were best described by a three-compartment model. Mean extrapolated peak (C0 ) plasma concentrations were 23.2 (± 5.93) μg/mL. Terminal half-life, volume of distribution at steady-state, mean residence time, and systemic clearance were characterized by a median (range) of 2.96 (2.46-4.71) h, 1.05 (0.943-1.21) L/kg, 1.98 (1.45-2.51) h, and 8.99 (6.68-10.8) mL/min/kg, respectively. Oral dose of MCBL was characterized by a median (range) terminal half-life, mean transit time, mean absorption time, and apparent oral clearance of 2.89 (2.21-4.88) h, 2.67 (1.80-2.87) h, 0.410 (0.350-0.770) h, and 16.5 (13.0-20) mL/min/kg. Bioavailability of orally administered MCBL was characterized by a median (range) of 54.4 (43.2-72.8)%. Guaifenesin plasma concentrations were below the limit of detection in all samples collected after the single intravenous dose of MCBL whereas they were detected for up to 24 h after the last dose of the multiple-dose oral regimen. This difference may be attributed to first-pass metabolism of MCBL to GGE after oral administration and may provide a means of differentiating the two routes of administration.
authors.affiliation: Department of Physiological Sciences, Florida Racing Laboratory, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Rumpler
authors.forename: P
authors.initials: P
authors.lastname: Colahan
authors.forename: R A
authors.initials: RA
authors.lastname: Sams
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004334:Drug Administration Schedule; D005100:Expectorants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006140:Guaifenesin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006736:Horses / Q000097:blood* / Q000378:metabolism; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D008721:Methocarbamol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D005100:Expectorants; D009125:Muscle Relaxants, Central; D008721:Methocarbamol; D006140:Guaifenesin