• 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. Animals—6 healthy alpacas. Procedures—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 and Clinical Relevance—Midazolam was well absorbed after IM administration, had a short duration of action, and induced moderate levels of sedation in alpacas. more »
  • Pharmacokinetics After Intravenous, Subcutaneous, and Oral Administration of Enrofloxacin to Alpacas

    Objective—To determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after PO, SC, and IV administration of enrofloxacin to alpacas. Animals—6 adult female alpacas. Procedure—A crossover design was used for administration of 3 single-dose treatments of enrofloxacin to alpacas, which was followed by an observational 14-day multiple-dose regimen. Single-dose treatments consisted of IV and SC administration of injectable enrofloxacin (5 mg/kg) and PO administration of enrofloxacin tablets (10 mg/kg) dissolved in grain to form a slurry. Plasma enrofloxacin concentrations were measured by use of high-performance liquid chromatography. The multiple-dose regimen consisted of feeding a mixture of crushed and moistened enrofloxacin tablets mixed with grain. Behavior, appetite, and fecal quality were monitored throughout the 14-day treatment regimen and for 71 additional days following treatment. Results—Mean half-life following IV, SC, and PO administration was 11.2, 8.7, and 16.1 hours, respectively. For SC and PO administration, mean total systemic availability was 90.18% and 29.31%, respectively; mean maximum plasma concentration was 3.79 and 1.81 µg/mL, respectively; and area under the curve (AUC) was 50.05 and 33.97 (µg × h)/mL, respectively. The SC or PO administration of a single dose of enrofloxacin yielded a ratio for AUC to minimum inhibitory concentration > 100 for many grampositive and gram-negative bacterial pathogens common to camelids. Conclusions and Clinical Relevance—The administration of enrofloxacin (5 mg/kg, SC, or 10 mg/kg, PO) may be appropriate for antimicrobial treatment of alpacas. more »
  • Plasma Concentrations of Fenbendazole (FBZ) and Oxfendazole in Alpacas (Lama pacos) After Single Intravenous and Oral Dosing of FBZ

    The objective of this study was to determine plasma pharmacokinetics and bioavailability of fenbendazole (FBZ) and oxfendazole (OFZ) after intravenous (iv) and oral administrations of FBZ (5 mg/kg) to alpacas. Plasma concentrations of FBZ and OFZ after administration of FBZ iv and orally (5 mg/kg) were determined by high-performance liquid chromatography with ultraviolet detection. Total clearance (CL) of FBZ was 16.5±4 mL/kg/min (range: 4–31 mL/kg/min), and steady-state volume of distribution (Vdss) was 3.3±1 L/kg (range: 1.7–7.4 L/kg). The terminal phase half-life of FBZ after iv administration was 5.9±3.8 hours (range: 0.8–20 hours). After oral administration, the FBZ terminal phase half-life was 23±5 hours (range: 9–37 hours) and the systemic bioavailability of FBZ was 16%±6% (range: 1%–41%). Peak FBZ concentrations after oral administration were 0.13±0.05 µg/mL (range: 0.05–0.28 µg/mL) at 10 hours (range: 8–12 hours). Peak plasma OFZ concentrations after oral dosing with FBZ (5 mg/kg) were 0.14±0.05 µg/mL (0.05–0.3 µg/mL) at 24±7 hours (range: 12–48 hours). FBZ clearance is lower in comparison to that of other species. Systemic availability of FBZ after oral administration is low after oral dosing. Metabolites of FBZ produced by alpacas are similar to those observed in other species. more »