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1.
The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine‐3 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine‐6 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4 ng/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady‐state and systemic clearance ranged from 9.40 to 16.9 L/kg and 23.3 to 32.4 ml min?1 kg?1, respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites.  相似文献   

2.
Nonsteroidal anti‐inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine‐sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5‐mg/kg dose of KT via each route of administration. Plasma was collected up to 48 h postadministration and analyzed for KT concentration using HPLC/MS/MS. Noncompartmental analysis of i.v. dosage indicated a mean plasma clearance of 8.4 (mL/min)/kg and an estimated mean volume of distribution at steady‐state of 0.77 L/kg. Noncompartmental analysis of i.v., i.m., and p.o. dosages indicated mean residence times of 2.0, 2.6, and 7.1 h, respectively. The drug was rapidly absorbed after i.m. and p.o. administration, and mean bioavailability was 71% and 57% for i.m. and p.o. administration, respectively. Adverse effects were not observed after i.v., i.m., and p.o. administration. More studies are needed to evaluate the analgesic and anti‐inflammatory properties of KT in horses.  相似文献   

3.
Knych, H. K., Casbeer, H. C., McKemie, D. S., Arthur, R. M. Pharmacokinetics and pharmacodynamics of butorphanol following intravenous administration to the horse. J. vet. Pharmacol. Therap.  36 , 21–30. Butorphanol is a narcotic analgesic commonly used in horses. Currently, any detectable concentration of butorphanol in biological samples collected from performance horses is considered a violation. The primary goal of the study reported here was to update the pharmacokinetics of butorphanol following intravenous administration, utilizing a highly sensitive liquid chromatography‐mass spectrometry (LC‐MS) assay that is currently employed in many drug‐testing laboratories. An additional objective was to characterize behavioral and cardiac effects following administration of butorphanol. Ten exercised adult horses received a single intravenous dose of 0.1 mg/kg butorphanol. Blood and urine samples were collected at time 0 and at various times for up to 120 h and analyzed using LC‐MS. Mean ± SD systemic clearance, steady‐state volume of distribution, and terminal elimination half‐life were 11.5 ± 2.5 mL/min/kg, 1.4 ± 0.3 L/kg, and 5.9 ± 1.5 h, respectively. Butorphanol plasma concentrations were below the limit of detection (LOD) (0.01 ng/mL) by 48 h post administration. Urine butorphanol concentrations were below the LOD (0.05 ng/mL) of the assay in seven of 10 horses by 120 h post drug administration. Following administration, horses appeared excited as noted by an increase in heart rate and locomotion. Gastrointestinal sounds were markedly decreased for up to 24 h.  相似文献   

4.
KuKanich, B. Pharmacokinetics of acetaminophen, codeine, and the codeine metabolites morphine and codeine‐6‐glucuronide in healthy Greyhound dogs. J. vet. Pharmacol. Therap. 33 , 15–21. The purpose of this study was to determine the pharmacokinetics of codeine and the active metabolites morphine and codeine‐6‐glucuronide after i.v. codeine administration and the pharmacokinetics of acetaminophen (APAP), codeine, morphine, and codeine‐6‐glucuronide after oral administration of combination product containing acetaminophen and codeine to dogs. Six healthy Greyhound dogs were administered 0.734 mg/kg codeine i.v. and acetaminophen (10.46 mg/kg mean dose) with codeine (1.43 mg/kg mean dose) orally. Blood samples were collected at predetermined time points for the determination of codeine, morphine, and codeine‐6‐glucuronide plasma concentrations by LC/MS and acetaminophen by HPLC with UV detection. Codeine was rapidly eliminated after i.v. administration (T½ = 1.22 h; clearance = 29.94 mL/min/kg; volume of distribution = 3.17 L/kg) with negligible amounts of morphine present, but large amounts of codeine‐6‐glucuronide (Cmax = 735.75 ng/mL) were detected. The oral bioavailability of codeine was 4%, morphine concentrations were negligible, but large amounts of codeine‐6‐glucuronide (Cmax = 1952.86 ng/mL) were detected suggesting substantial first pass metabolism. Acetaminophen was rapidly absorbed (Cmax = 6.74 μg/mL; Tmax = 0.85 h) and eliminated (T½ = 0.96 h). In conclusion, the pharmacokinetics of codeine was similar to other opioids in dogs with a short half‐life, rapid clearance, large volume of distribution, and poor oral bioavailability. High concentrations of codeine‐6‐glucuronide were detected after i.v. and oral administration.  相似文献   

5.
The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long‐term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend®) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as pharmacodynamic assessment of the effect of plasma pergolide concentrations on plasma ACTH concentrations. Pergolide effectively decreased plasma ACTH concentration in aged horses with PPID, with similar pharmacokinetic properties as reported in young horses, including an approximate terminal half‐life of 24 h. Plasma ACTH concentration increased by 50% in 3/6 horses at 2 days and 6/6 horses 10 days after discontinuing drug administration. Pergolide was quantified in all horses at 2 days and in none at 10 days after last dose. In summary, after discontinuing pergolide treatment, plasma ACTH concentration increased while pergolide was still quantifiable in some horses. Once‐daily dosing of pergolide is likely appropriate in most horses with PPID for regulating the plasma ACTH concentration.  相似文献   

6.
Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL when administered at least 24 h prior to race time. In light of samples exceeding the regulatory threshold at 24 h postadministration, the primary goal of the study reported here was to update the pharmacokinetics of flunixin following intravenous administration, utilizing a highly sensitive liquid chromatography–mass spectrometry (LC‐MS). An additional objective was to characterize the effects of flunixin on COX‐1 and COX‐2 inhibition when drug concentrations reached the recommended regulatory threshold. Sixteen exercised adult horses received a single intravenous dose of 1.1 mg/kg. Blood samples were collected up to 72 h postadministration and analyzed using LC‐MS. Blood samples were collected from 8 horses for determination of TxB2 and PGE2 concentrations prior to and up to 96 h postflunixin administration. Mean systemic clearance, steady‐state volume of distribution and terminal elimination half‐life was 0.767 ± 0.098 mL/min/kg, 0.137 ± 0.12 L/kg, and 4.8 ± 1.59 h, respectively. Four of the 16 horses had serum concentrations in excess of the current ARCI recommended regulatory threshold at 24 h postadministration. TxB2 suppression was significant for up to 24 h postadministration.  相似文献   

7.
Equine herpes myeloencephalopathy, resulting from equine herpes virus type 1 (EHV‐1) infection, is associated with substantial morbidity and mortality in the horse. As compared to other antiviral drugs, such as acyclovir, ganciclovir has enhanced potency against EHV‐1. This study investigated the pharmacokinetics of ganciclovir and its oral prodrug, valganciclovir, in six adult horses in a randomized cross‐over design. Ganciclovir sodium was administered intravenously as a slow bolus at a dose of 2.5 mg/kg, and valganciclovir was administered orally at a dose of 1800 mg per horse. Intravenously administered ganciclovir disposition was best described by a three‐compartment model with a prolonged terminal half‐life of 72 ± 9 h. Following the oral administration of valganciclovir, the mean observed maximum serum ganciclovir concentration was 0.58 ± 0.37 μg/mL, and bioavailability of ganciclovir from oral valganciclovir was 41 ± 20%. Superposition predicted that oral dosing of 1800‐mg valganciclovir two times daily would fail to produce and maintain effective plasma concentrations of ganciclovir. However, superposition suggested that i.v. administration of ganciclovir at 2.5 mg/kg every 8 h for 24 h followed by maintenance dosing of 2.5 mg/kg every 12 h would maintain effective ganciclovir serum concentrations in most horses throughout the dosing interval.  相似文献   

8.
The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2‐amino‐5‐thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high‐performance liquid chromatography assay. The data were evaluated using noncompartmental pharmacokinetic analyses. The estimated plasma pharmacokinetic parameters were compared with the hypothetical minimum inhibitory concentration (MIC) values (0.125–2 μg/mL). The plasma and synovial fluid concentrations and area under the concentration–time curves (AUC) of cefquinome showed a dose‐dependent increase. After a first dose of cefquinome, the ranges for the mean plasma half‐life values (2.30–2.41 h), the mean residence time (1.77–2.25 h), the systemic clearance (158–241 mL/h/kg), and the volume of distribution at steady‐state (355–431 mL/kg) were consistent across dose levels and similar to those observed after multiple doses. Cefquinome did not accumulate after multiple doses. Cefquinome penetrated the synovial fluid with AUCsynovial fluid/AUCplasma ratios ranging from 0.57 to 1.37 after first and thirteenth doses, respectively. Cefquinome is well tolerated, with no adverse effects. The percentage of time for which the plasma concentrations were above the MIC was >45% for bacteria, with MIC values of ≤0.25, ≤0.5, and ≤1 μg/mL after the administration of 1, 2, and 4 or 6 mg/kg doses of CFQ at 12‐h intervals, respectively. Further studies are needed to determine the optimal dosage regimes in critically ill patients.  相似文献   

9.
Procaterol (PCR) is a beta‐2‐adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography–mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady‐state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half‐life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.  相似文献   

10.
The study objective was to compare butorphanol pharmacokinetics and physiologic effects following intravenous and subcutaneous administration in horses. Ten adult horses received 0.1 mg/kg butorphanol by either intravenous or subcutaneous injections, in a randomized crossover design. Plasma concentrations of butorphanol were measured at predetermined time points using highly sensitive liquid chromatography–tandem mass spectrometry assay (LC‐MS/MS). Demeanor and physiologic variables were recorded. Data were analyzed with multivariate mixed‐effect model on ranks (P ≤ 0.05). For subcutaneous injection, absorption half‐life and peak plasma concentration of butorphanol were 0.10 ± 0.07 h and 88 ± 37.4 ng/mL (mean ± SD), respectively. Bioavailability was 87%. After intravenous injection, mean ± SD butorphanol steady‐state volume of distribution and clearance was 1.2 ± 0.96 L/kg and 0.65 ± 0.20 L/kg/h, respectively. Terminal half‐lives for butorphanol were 2.31 ± 1.74 h and 5.29 ± 1.72 h after intravenous and subcutaneous administrations. Subcutaneous butorphanol reached and maintained target plasma concentrations >10 ng/mL for 2 ± 0.87 h (Mean ± SD), with less marked physiologic and behavioral effects compared to intravenous injection. Subcutaneous butorphanol administration is an acceptable alternative to the intravenous route in adult horses.  相似文献   

11.
The anti‐anxiety and calming effects following activation of the GABA receptor have been exploited in performance horses by administering products containing GABA. The primary goal of the study reported here was to describe endogenous concentrations of GABA in horses and the pharmacokinetics, selected pharmacodynamic effects, and CSF concentrations following administration of a GABA‐containing product. The mean (±SD) endogenous GABA level was 36.4 ± 12.5 ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650 mg). Blood, urine, and cerebrospinal fluid (n = 2) samples were collected at time 0 and at various times for up to 48 h and analyzed using LC‐MS. Plasma clearance and volume of distribution was 155.6 and 147.6 L/h and 0.154 and 7.39 L for the central and peripheral compartments, respectively. Terminal elimination half‐life was 22.1 (intravenous) and 25.1 (oral) min. Oral bioavailability was 9.81%. Urine GABA concentrations peaked rapidly returning to baseline levels by 3 h. Horses appeared behaviorally unaffected following oral administration, while sedative‐like changes following intravenous administration were transient. Heart rate was increased for 1 h postintravenous administration, and gastrointestinal sounds decreased for approximately 30 min following both intravenous and oral administration. Based on a limited number of horses and time points, exogenously administered GABA does not appear to enter the CSF to an appreciable extent.  相似文献   

12.
Flunixin meglumine (FM) is a commonly used Nonsteroidal anti‐inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti‐inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)‐induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM. Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed. Ketorolac tromethamine and FM suppressed LPS‐induced Thromboxane B2 (TXB2) and Prostaglandin E2 (PGE2) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS‐induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti‐inflammatory and analgesic effects of KT is warranted.  相似文献   

13.
Romifidine is an alpha‐2 adrenergic agonist used for sedation and analgesia in horses. As it is a prohibited substance, its purported use at low doses in performance horses necessitates further study. The primary goal of the study reported here was to describe the serum concentrations and pharmacokinetics of romifidine following low‐dose administration immediately prior to exercise, utilizing a highly sensitive liquid chromatography–tandem mass spectrometry assay that is currently employed in many drug testing laboratories. An additional objective was to describe changes in heart rate and rhythm following intravenous administration of romifidine followed by exercise. Eight adult Quarter Horses received a single intravenous dose of 5 mg (0.01 mg/kg) romifidine followed by 1 h of exercise. Blood samples were collected and drug concentrations measured at time 0 and at various times up to 72 h. Mean ± SD systemic clearance, steady‐state volume of distribution and terminal elimination half‐life were 34.1 ± 6.06 mL/min/kg and 4.89 ± 1.31 L/kg and 3.09 ± 1.18 h, respectively. Romifidine serum concentrations fell below the LOQ (0.01 ng/mL) and the LOD (0.005 ng/mL) by 24 h postadministration. Heart rate and rhythm appeared unaffected when a low dose of romifidine was administered immediately prior to exercise.  相似文献   

14.
The neurokinin‐1 (NK) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood and likely under‐recognized in horses. Use of NK‐1 receptor antagonists in horses has not been reported. The purpose of this study was to determine the pharmacokinetic profile of maropitant in seven adult horses after single intravenous (IV; 1 mg/kg) and intragastric (IG; 2 mg/kg) doses. A randomized, crossover design was performed. Serial blood samples were collected after dosing; maropitant concentrations were measured using LC‐MS/MS. Pharmacokinetic parameters were determined using noncompartmental analysis. The mean plasma maropitant concentration 3 min after IV administration was 800 ± 140 ng/ml, elimination half‐life was 10.37 ± 2.07 h, and volume of distribution was 6.54 ± 1.84 L/kg. The maximum concentration following IG administration was 80 ± 40 ng/ml, and elimination half‐life was 9.64 ± 1.27 hr. Oral bioavailability was variable at 13.3 ± 5.3%. Maropitant concentrations achieved after IG administration were comparable to those in small animals. Concentrations after IV administration were lower than in dogs and cats. Elimination half‐life was longer than in dogs and shorter than in cats. This study is the basis for further investigations into using maropitant in horses.  相似文献   

15.
This study aimed to investigate both the pharmacokinetic behavior and tolerance of methotrexate (MTX) in horses to design a specific dosing regimen as a new immunomodulatory drug for long-term treatment. To determine the primary plasma pharmacokinetic variables after single intravenous, subcutaneous or oral administration, six horses were administered 0.3 mg/kg MTX in a crossover design study. After a 10-week washout, MTX was administered subcutaneously to three of the six previously treated horses at a dose of 0.3 mg/kg once per week for 3 months. In both studies, MTX and metabolite concentrations were measured using LC-MS/MS. The absolute bioavailability of MTX was 73% following subcutaneous administration but less than 1% following oral administration. The plasma clearance was 1.54 ml min−1 kg−1 (extraction ratio = 2%). After 24 hr, plasma concentrations were below the LOQ. No adverse effects were noted except for a moderate reversible elevation in liver enzymes (GLDH). With regards to the main metabolites of MTX, very low concentrations of 7-hydroxy-MTX were found, whereas polyglutamated forms (mainly short chains) were found in red blood cells. A subcutaneous dose of 0.2 mg kg−1 week−1 may be safe and relevant in horses, although this has yet to be clinically confirmed.  相似文献   

16.
This study aimed to investigate the effect of diet and dose on the pharmacokinetics of omeprazole in the horse. Six horses received two doses (1 and 4 mg/kg) of omeprazole orally once daily for 5 days. Each dose was evaluated during feeding either a high‐grain/low‐fibre (HG/LF) diet or an ad libitum hay (HAY) diet in a four‐way crossover design. Plasma samples were collected for pharmacokinetic analysis on days 1 and 5. Plasma omeprazole concentrations were determined by ultra‐high pressure liquid chromatography–mass spectrometry. In horses being fed the HG/LF diet, on day 1, the area under the curve (AUC) and maximal plasma concentration (Cmax) were higher on the 4 mg/kg dose than on the 1 mg/kg dose. The AUC was higher on day 5 compared to day 1 with the 4 mg/kg dose on the HG/LF diet. On days 1 and 5, the AUC and Cmax were higher in horses being fed the HG/LF diet and receiving the 4 mg/kg dose than in horses being fed the HAY diet and receiving the 1 mg/kg dose. These findings suggest that both dose and diet may affect pharmacokinetic variables of omeprazole in the horse.  相似文献   

17.
The objectives were to document the pharmacokinetics of intravenous, enteric‐coated oral and plain oral omeprazole in fasted horses and to investigate the impact of feeding on the bioavailability of an enteric‐coated omeprazole. Twelve horses received four treatments: intravenous omeprazole (0.5 mg/kg) in the fasted state (IV‐Fasted), enteric‐coated omeprazole (4 mg/kg) orally in the fasted state (ECO‐Fasted), enteric‐coated omeprazole (4 mg/kg) orally in the fed state (ECO‐Fed) and plain omeprazole (4 mg/kg) orally in the fasted state (PL‐Fasted). Plasma omeprazole concentrations were determined by UHPLC‐MS. Bioavailability was higher (P = 0.038) in the ECO‐Fasted group (21.5 [9.0–27.7]%) than the PL‐Fasted group (10.1 [7.7–13.3]%). Similarly, AUC0‐∞ was higher in the ECO‐Fasted group than the PL‐Fasted group (P = 0.027). No significant differences were present between the ECO‐Fasted and ECO‐Fed groups with regards to bioavailability, Cmax, Tmax or AUC0‐∞. When the half‐life data from the oral formulations was pooled, it was longer than that observed in the IV‐Fasted group (100 [73–118] min) and 35 [34‐39] min, respectively; P < 0.0001). Bioavailability of enteric‐coated omeprazole was higher than previously reported and feeding had minimal impact. Bioavailability of plain omeprazole was approximately half that of enteric‐coated omeprazole. The longer half‐life observed following oral administration was consistent with the flip‐flop effect and has not previously been described for omeprazole in the horse.  相似文献   

18.
The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α‐hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one‐compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single‐dose administration of alprazolam were as follows: Cmax 14.76 ± 3.72 ng/mL and area under the curve (AUC0–∞) 358.77 ± 76.26 ng·h/mL. Median (range) Tmax was 3 h (1–12 h). Alpha‐hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (Cmax 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted.  相似文献   

19.
Acepromazine is a tranquilizer used commonly in equine medicine. This study describes serum and urine concentrations and the pharmacokinetics and pharmacodynamics of acepromazine following intravenous, oral, and sublingual (SL) administration. Fifteen exercised adult Thoroughbred horses received a single intravenous, oral, and SL dose of 0.09 mg/kg of acepromazine. Blood and urine samples were collected at time 0 and at various times for up to 72 hr and analyzed for acepromazine and its two major metabolites (2‐(1‐hydroxyethyl) promazine and 2‐(1‐hydroxyethyl) promazine sulfoxide) using liquid chromatography–tandem mass spectrometry. Acepromazine was also incubated in vitro with whole equine blood and serum concentrations of the parent drug and metabolites determined. Acepromazine was quantitated for 24 hr following intravenous administration and 72 hr following oral and SL administration. Results of in vitro incubations with whole blood suggest additional metabolism by RBCs. The mean ± SEM elimination half‐life was 5.16 ± 0.450, 8.58 ± 2.23, and 6.70 ± 2.62 hr following intravenous, oral, and SL administration, respectively. No adverse effects were noted and horses appeared sedate as noted by a decrease in chin‐to‐ground distance within 5 (i.v.) or 15 (p.o. and SL) minutes postadministration. The duration of sedation lasted 2 hr. Changes in heart rate were minimal.  相似文献   

20.
The purpose of this study was to determine the pharmacokinetics of the FDA‐approved labeled dose of diclazuril and compare it to a low dose in plasma and CSF in adult horses. During each research period, six healthy adult horses received 0.5 mg/kg of 1.56% diclazuril pellets (ProtazilTM, Merck Animal Health) compared to the approved labeled dose of 1 mg/kg orally once in two separate phases. A dose of 0.5 mg/kg was calculated to each horse's weight. Blood was then collected immediately before diclazuril administration and then at regular intervals up to a 168 h. After the last blood collection following the single dose at hour 168, a once daily oral dose was administered for the next 10 days to ensure the drug's concentration reached steady‐state. To determine the CSF concentration at steady‐state, CSF samples were collected after the 9th oral dose. Blood was then collected after the 10th dose and then at regular intervals up to 168 h. A washout period of 4 weeks was allowed before repeating this protocol for the FDA‐labeled dose at 1 mg/kg. Plasma and CSF samples were analyzed by high‐pressure liquid chromatography. A one‐compartment pharmacokinetic model with first‐order oral absorption was fitted to the single administration data. Steady‐state pharmacokinetics was performed using noncompartmental analysis for steady‐state analysis. The mean (standard deviation) concentration of diclazuril in CSF following the low dose was 26 ng/mL (5 ng/mL), while CSF in the FDA‐labeled dose was 25 ng/mL (4 ng/mL), P = 0.3750. Substantial accumulation in plasma occurred at steady‐state after the 10th dose for both doses. The results of this study show that diclazuril pellets given at the approved label dose and a lower dose both produce similar plasma drug concentrations at steady‐state and attain plasma and CSF concentrations known to inhibit Sarcocystis neurona in cell culture.  相似文献   

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