The Pharmacokinetics and Pharmacodynamics of Midazolam in Alpacas

Aarnes TK, Fry PR, Hubbell JAE, Bednarski RM, Lerche P, Lakritz J
The Ohio State University, Columbus, OH, USA

The objective of the study was to determine midazolam pharmacokinetics in adult alpacas after IV and IM administration.

Six alpacas (mean age 4.3 years, mean body weight 64.5 kg, 3 males, 3 females) were given midazolam (0.5 mg kg-1) on two separate occasions (once IV, once IM) in a randomized crossover design. Samples of jugular venous blood were obtained via catheter before and at standardized intervals for 24 hours after administration. Midazolam concentrations were determined using tandem liquid chromatography-mass spectrometry. Pharmacokinetic analysis was conducted using a WinNonlin proprietary program. Sedative effects were assessed using a 4-point scale that ranged from no sedation to obvious sedation with recumbency. Time to onset, time to peak, and duration of sedation were recorded. Sedation data were analyzed using a Wilcoxon signed rank test (p less than 0.05).

Calculated median maximum concentration was 1394 ng mL-1 (range 1150-1503) after IV midazolam. Median maximum concentration was 411 ng mL-1 (range 217-675) after IM midazolam with maximum concentrations occurring between 5 and 30 minutes. Median distribution half-life was 18.7 minutes (range 13-47) and median elimination halflife was 98 minutes (range 67-373) after IV administration. Bioavailability of midazolam after IM administration was 92%. Peak sedation occurred at 0.4 minutes (IV) and 15 minutes (IM). Obvious sedation was present for up to 75 minutes (IV). Sedation was significantly greater in the IV group.

Midazolam has relatively short distribution and elimination half-lives, and produces moderate levels of sedation in alpacas.

Publication resulting from this work.

Turi K. Aarnes, DVM, MS; Pamela R. Fry, DVM, MS; John A. E. Hubbell, DVM, MS; Richard M. Bednarski, DVM, MS; Phillip Lerche, BVSc, PhD; Wei Chen, PhD; Di Bei, PhD; Zhongfa Liu, PhD; Jeffrey Lakritz, DVM, PhD, Pharmacokinetics and pharmacodynamics of midazolam after intravenous and intramuscular administration in alpacas AJVR, Vol 74, No. 2, February 2013