{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:40:21Z","timestamp":1774690821186,"version":"3.50.1"},"reference-count":42,"publisher":"American Veterinary Medical Association (AVMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>OBJECTIVE<\/jats:bold> To determine the pharmacokinetic and pharmacodynamic effects of midazolam following IV and IM administration in sheep.<\/jats:p>\n<jats:p><jats:bold>ANIMALS<\/jats:bold> 8 healthy adult rams.<\/jats:p>\n<jats:p><jats:bold>PROCEDURES<\/jats:bold> Sheep were administered midazolam (0.5 mg\/kg) by the IV route and then by the IM route 7 days later in a crossover study. Physiologic and behavioral variables were assessed and blood samples collected for determination of plasma midazolam and 1-hydroxymidazolam (primary midazolam metabolite) concentrations immediately before (baseline) and at predetermined times for 1,440 minutes after midazolam administration. Pharmacokinetic parameters were calculated by compartmental and noncompartmental methods.<\/jats:p>\n<jats:p><jats:bold>RESULTS<\/jats:bold> Following IV administration, midazolam was rapidly and extensively distributed and rapidly eliminated; mean \u00b1 SD apparent volume of distribution, elimination half-life, clearance, and area under the concentration-time curve were 838 \u00b1 330 mL\/kg, 0.79 \u00b1 0.44 hours, 1,272 \u00b1 310 mL\/h\/kg, and 423 \u00b1 143 h\u00b7ng\/mL, respectively. Following IM administration, midazolam was rapidly absorbed and bioavailability was high; mean \u00b1 SD maximum plasma concentration, time to maximum plasma concentration, area under the concentration-time curve, and bioavailability were 820 \u00b1 268 ng\/mL, 0.46 \u00b1 0.26 hours, 1,396 \u00b1 463 h\u00b7ng\/mL, and 352 \u00b1 148%, respectively. Respiratory rate was transiently decreased from baseline for 15 minutes after IV administration. Times to peak sedation and ataxia after IV administration were less than those after IM administration.<\/jats:p>\n<jats:p><jats:bold>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:bold> Results indicated midazolam was a suitable short-duration sedative for sheep, and IM administration may be a viable alternative when IV administration is not possible.<\/jats:p>","DOI":"10.2460\/ajvr.78.5.539","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T17:56:14Z","timestamp":1493142974000},"page":"539-549","source":"Crossref","is-referenced-by-count":19,"title":["Pharmacokinetics and pharmacodynamics of midazolam following intravenous and intramuscular administration to sheep"],"prefix":"10.2460","volume":"78","author":[{"given":"Bradley T.","family":"Simon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth 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