title: Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses.
abstract: OBJECTIVE
  To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses.
  
  
  METHODS
  6 healthy adult horses.
  
  
  METHODS
  Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects.
  
  
  RESULTS
  In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration.
  
  
  CONCLUSIONS
  Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.
authors.affiliation: Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, 70803, USA. rlinardi@vet.upenn.edu
authors.forename: Renata L
authors.initials: RL
authors.lastname: Linardi
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Stokes
authors.forename: Michael L
authors.initials: ML
authors.lastname: Keowen
authors.forename: Steven A
authors.initials: SA
authors.lastname: Barker
authors.forename: Giselle L
authors.initials: GL
authors.lastname: Hosgood
authors.forename: Charles R
authors.initials: CR
authors.lastname: Short
mesh_terms: D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D006207:Half-Life; D006736:Horses / Q000097:blood*; D007275:Injections, Intravenous; D008691:Methadone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone