Pharmacokinetics of intramuscular maropitant in pigs (Sus scrofa domesticus).

Pigs are at risk of vomiting from medical conditions as well as the emetic side effects of drugs administered for peri-operative manipulations, but there is a lack of pharmacokinetic data for potential anti-emetic therapies, such as maropitant, in this species. The main objective of this study was to estimate plasma pharmacokinetic parameters for maropitant in pigs after a single intramuscular (IM) administration dosed at 1.0 mg/kg. A secondary objective was to estimate pilot pharmacokinetic parameters in pigs after oral (PO) administration at 2.0 mg/kg. Maropitant was administered to six commercial pigs at a dose of 1.0 mg/kg IM. Plasma samples were collected over 72 h. After a 7-day washout period, two pigs were administered maropitant at a dose of 2.0 mg/kg PO. Maropitant concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive pharmacokinetics parameters. No adverse events were noted in any of the study pigs after administration. Following single IM administration, maximum plasma concentration was estimated at 412.7 ± 132.0 ng/mL and time to maximum concentration ranged from 0.083 to 1.0 h. Elimination half-life was estimated at 6.7 ± 1.28 h, and mean residence time was 6.1 ± 1.2 h. Volume of distribution after IM administration was 15.9 L/kg. Area under the curve was 1336 ± 132.0 h*ng/mL. The relative bioavailability of PO administration was noted to be 15.5% and 27.2% in the two pilot pigs. The maximum systemic concentration observed in the study pigs after IM administration was higher than what was observed after subcutaneous administration in dogs, cats, or rabbits. The achieved maximum concentration exceeded the concentrations for anti-emetic purposes in dogs and cats; however, a specific anti-emetic concentration is currently not known for pigs. Further research is needed into the pharmacodynamics of maropitant in pigs to determine specific therapeutic strategies for this drug.

The pharmacokinetics and pharmacodynamics of midazolam after intravenous administration to donkeys (Equus africanus asinus).

The pharmacokinetics and pharmacodynamics of midazolam were studied in eight 1-to-3-year-old healthy gelded donkeys. Blood samples were obtained. Heart rate, respiratory rate, rectal temperature, sedation/excitement, ataxia, and response to tactile and auditory stimuli were recorded at baseline until 48 hours after intravenous (IV) midazolam (0.1 mg/kg) administration. Plasma midazolam and 1-hydroxymidazolam were measured using reversed-phase high-performance liquid chromatography. Pharmacokinetic variables were calculated using non-compartmental analysis. Physiologic data were analyzed using a mixed-effects model followed by Dunnett's test and behavioral data were analyzed using a Friedman test then a Dunn's test; P < 0.05 was considered significant. Midazolam was detectable for up to 60 minutes post-treatment in 7 donkeys. The median total body clearance, volume of distribution at steady state, elimination half-life, and area under concentration-time profile were 1210 mL/kg/h, 359 mL/kg, 0.27 hours, and 82.7 h × ng/mL, respectively. 1-hydroxymidazolam was detected (29 to 105 ng/mL) between 5 to 15 minutes post-treatment in 4 donkeys. Compared to baseline, rectal temperature and ataxia increased from 90 to 720 minutes (P ≤ 0.038) and 3 to 15 minutes (P ≤ 0.024) post-treatment, respectively. No other parameters showed statistically significant differences. Healthy donkeys cleared midazolam rapidly from plasma after IV administration. Transient ataxia and recumbency without sedation were observed.

La pharmacocinétique et la pharmacodynamique du midazolam ont été étudiées chez huit ânes hongres en bonne santé âgés de 1 à 3 ans. Des échantillons de sang ont été obtenus. La fréquence cardiaque, la fréquence respiratoire, la température rectale, la sédation/excitation, l'ataxie et la réponse aux stimuli tactiles et auditifs ont été enregistrées au départ jusqu'à 48 heures après l'administration intraveineuse (IV) de midazolam (0,1 mg/kg). Le midazolam plasmatique et le 1-hydroxymidazolam ont été mesurés par chromatographie liquide haute performance en phase inversée. Les variables pharmacocinétiques ont été calculées à l'aide d'une analyse non compartimentale. Les données physiologiques ont été analysées à l'aide d'un modèle à effets mixtes suivi du test de Dunnett et les données comportementales ont été analysées à l'aide d'un test de Friedman puis d'un test de Dunn; P < 0,05 était considéré comme significatif. Le midazolam était détectable jusqu'à 60 minutes après le traitement chez sept ânes. La clairance corporelle totale médiane, le volume de distribution à l'état d'équilibre, la demi-vie d'élimination et l'aire sous le profil concentration-temps étaient respectivement de 1210 mL/kg par heure, 359 mL/kg, 0,27 heure et 82,7 heures × ng/mL. Le 1-hydroxymidazolam a été détecté (29 à 105 ng/mL) entre 5 et 15 minutes après le traitement chez quatre ânes. Par rapport au départ, la température rectale et l'ataxie ont augmenté de 90 à 720 minutes (P ≤ 0,038) et de 3 à 15 minutes (P ≤ 0,024) après le traitement, respectivement. Aucun autre paramètre n'a montré de différences statistiquement significatives. Des ânes en bonne santé ont rapidement éliminé le midazolam du plasma après administration IV. Une ataxie transitoire et un décubitus sans sédation ont été observés.(Traduit par Docteur Serge Messier).

Pharmacokinetic and pharmacodynamic properties of pantoprazole in calves.

Introduction: Development of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant species. Proton pump inhibitors, such as pantoprazole, are widely used in humans and companion animals. Their efficacy in ruminant species is undetermined. The objectives of this study were to 1) estimate the plasma pharmacokinetic parameters for pantoprazole in neonatal calves after three days of intravenous (IV) or subcutaneous (SC) administration, and 2) measure the effect pantoprazole had on abomasal pH over the treatment period. Methods: Pantoprazole was administered to 6 Holstein-Angus cross bull calves at a dose of 1 mg/kg (IV) or 2 mg/kg (SC), once a day (every 24 h) for three days. Plasma samples were collected over a 72 h period and analyzed via HPLC-UV for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Abomasal (n= 8) samples were collected via abomasal cannulas over a 12 h period, per calf per day. Abomasal pH was determined via a bench top pH analyzer. Results: Following Day 1 of IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 199.9 mL/kg/h, 1.44 h, and 0.51 L/kg, respectively. On Day 3 of IV administration, the reported values were 192.9 mL/kg/h, 2.52 h, and 1.80 L/kg mL, respectively. Elimination half-life and volume of distribution (V/F) of pantoprazole following SC administration were estimated at 1.81 h and 0.55 L/kg, respectively, on Day 1; and 2.99 h and 2.82 L/kg, respectively, on Day 3. Discussion: The reported values for IV administration were similar to those previously reported in calves. SC administration appears to be well absorbed and tolerated. The sulfone metabolite was detectable for 36 h after the last administration for both routes. Abomasal pH was significantly higher than the pre-pantoprazole pH 4, 6, and 8 h after administration in both the IV and SC groups. Further studies of pantoprazole as a treatment/preventative for abomasal ulcers are warranted.