Pharmacokinetics and pharmacodynamics of midazolam after intravenous and intramuscular administration in alpacas.
OBJECTIVE
To determine pharmacokinetic and pharmacodynamic properties of midazolam after IV and IM administration in alpacas.


METHODS
6 healthy alpacas.


METHODS
Midazolam (0.5 mg/kg) was administered IV or IM in a randomized crossover design. Twelve hours prior to administration, catheters were placed in 1 (IM trial) or both (IV trial) jugular veins for drug administration and blood sample collection for determination of serum midazolam concentrations. Blood samples were obtained at intervals up to 24 hours after IM and IV administration. Midazolam concentrations were determined by use of tandem liquid chromatography-mass spectrometry.


RESULTS
Maximum concentrations after IV administration (median, 1,394 ng/mL [range, 1,150 to 1,503 ng/mL]) and IM administration (411 ng/mL [217 to 675 ng/mL]) were measured at 3 minutes and at 5 to 30 minutes, respectively. Distribution half-life was 18.7 minutes (13 to 47 minutes) after IV administration and 41 minutes (30 to 80 minutes) after IM administration. Elimination half-life was 98 minutes (67 to 373 minutes) and 234 minutes (103 to 320 minutes) after IV and IM administration, respectively. Total clearance after IV administration was 11.3 mL/min/kg (6.7 to 13.9 mL/min/kg), and steady-state volume of distribution was 525 mL/kg (446 to 798 mL/kg). Bioavailability of midazolam after IM administration was 92%. Peak onset of sedation occurred at 0.4 minutes (IV) and 15 minutes (IM). Sedation was significantly greater after IV administration.


CONCLUSIONS
Midazolam was well absorbed after IM administration, had a short duration of action, and induced moderate levels of sedation in alpacas.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA. aarnes.1@osu.edu
Turi K
TK
Aarnes
Pamela R
PR
Fry
John A E
JA
Hubbell
Richard M
RM
Bednarski
Phillip
P
Lerche
Wei
W
Chen
Di
D
Bei
Zhongfa
Z
Liu
Jeffrey
J
Lakritz
D061605:Administration, Intravenous / Q000662:veterinary; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002161:Camelids, New World / Q000502:physiology*; D002853:Chromatography, Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular / Q000662:veterinary; D008297:Male; D013058:Mass Spectrometry / Q000662:veterinary; D008874:Midazolam / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D056152:Respiratory Rate / Q000187:drug effects*
D006993:Hypnotics and Sedatives; D008874:Midazolam