title: Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs.
abstract: Midazolam, a water-soluble benzodiazepine tranquilizer, has been considered by some veterinary anaesthesiologists to be suitable as a combination anaesthetic agent when administered concurrently with ketamine because of its water solubility and miscibility with ketamine. However, the pharmacokinetics of midazolam have not been extensively described in the dog. Twelve clinically healthy mixed breed dogs (22.2-33.4 kg) were divided into two groups at random and were administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) either as an intravenous bolus over 30 s (group 1) or as an i.v. infusion in 0.9% NaCl (2 ml/kg) over 15 min. Blood samples were obtained immediately before the drugs were injected and periodically for 6 h afterwards. Serum concentrations were determined using gas chromatography with electron-capture detection. Serum concentrations were best described using a two-compartment open model and indicated a t1/2-alpha of 1.8 min and t1/2-beta of 27.8 min after i.v. bolus, and t1/2-alpha of 1.35 min and t1/2-beta of 31.6 min after i.v. infusion. The calculated pharmacokinetic coefficient B was significantly smaller after i.v. infusion (429 +/- 244 ng/ml) than after i.v. bolus (888 +/- 130 ng/ml, P = 0.004). Furthermore, AUC was significantly smaller after i.v. infusion (29,800 +/- 6120 ng/h/ml) than after i.v. bolus (42,500 +/- 8460 ng/h/ml, P < 0.05), resulting in a larger ClB after i.v. infusion (17.4 +/- 4.00 ml/min/kg than after i.v. bolus (12.1 +/- 2.24 ml/min/kg, P < 0.05). No other pharmacokinetic value was significantly affected by rate of intravenous administration.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station 77843.
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.forename: J D
authors.initials: JD
authors.lastname: Jacobson
authors.forename: S M
authors.initials: SM
authors.lastname: Hartsfield
mesh_terms: D000758:Anesthesia / Q000662:veterinary; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects; D004285:Dogs / Q000378:metabolism*; D005260:Female; D007262:Infusions, Intravenous / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D007649:Ketamine; D008874:Midazolam