Pharmacokinetics of difloxacin and its concentration in body fluids and endometrial tissues of mares after repeated intragastric administration

Pharmacokinetics of difloxacin and its distribution within the body fluids and endometrium of 6 mares were studied after intragastric (IG) administration of 5 individual doses. Difloxacin concentrations were serially measured in serum, urine, peritoneal fluid, synovial fluid, cerebrospinal fluid, and endometrium over 120 h. Bacterial susceptibility to difloxacin was determined for 174 equine pathogens over a 7-month period. Maximum serum concentration (Cmax) was 2.25 +/- 0.70 microg/mL at 3.12 +/- 2.63 h and Cmax after the 5th dose was 2.41 +/- 0.86 microg/mL at 97.86 +/- 1.45 h. The mean elimination half-life (t(1/2)) was 8.75 +/- 2.77 h and area under the serum concentration versus time curve (AUC) was 25.13 +/- 8.79 microg h/mL. Highest mean synovial fluid concentration was 1.26 +/- 0.49 microg/mL at 100 h. Highest mean peritoneal fluid concentration was 1.50 +/- 0.56 microg/mL at 98 h. Highest mean endometrial concentration was 0.78 +/- 0.48 microg/g at 97.5 h. Mean cerebrospinal fluid concentration was 0.87 +/- 0.52 microg/mL at 99 h. Highest mean urine concentration was 92.05 +/- 30.35 microg/mL at 104 h. All isolates of Salmonella spp. and Pasteurella spp. were susceptible. In general, gram-negative organisms were more susceptible than gram-positives. Difloxacin appears to be safe, adequately absorbed, and well distributed to body fluids and endometrial tissues of mares and may be useful in the treatment of susceptible bacterial infections in adult horses.     

Effect of general anesthesia and minor surgical trauma on urine and serum measurements in horses

OBJECTIVE: To characterize the effect of general anesthesia and minor surgery on renal function in horses. ANIMALS: 9 mares with a mean (+/- SE) age and body weight of 9+/-2 years and 492+/-17 kg, respectively. PROCEDURE: The day before anesthesia, urine was collected (catheterization) for 3 hours to quantitate baseline values, and serum biochemical analysis was performed. The following day, xylazine (1.1 mg/kg, IV) was administered, and general anesthesia was induced 5 minutes later with diazepam (0.04 mg/kg, IV) and ketamine (2.2 mg/kg, IV). During 2 hours of anesthesia with isoflurane, Paco2 was maintained between 48 and 52 mm Hg, and mean arterial blood pressure was between 70 and 80 mm Hg. Blood and urine were collected at 30, 60, and 120 minutes during and at 1 hour after anesthesia. RESULTS: Baseline urine flow was 0.92+/-0.17 ml/kg/h and significantly increased at 30 and 60 minutes after xylazine administration (2.14+/-0.59 and 2.86+/-0.97 ml/kg/h respectively) but returned to baseline values by the end of anesthesia. Serum glucose concentration increased from 12+/-4 to 167+/-8 mg/dl at 30 minutes. Glucosuria was not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Transient hyperglycemia and an increase in rine production accompanies a commonly used anesthetic technique for horses. The increase in urine flow is not trivial and should be considered in anesthetic management decisions. With the exception of serum glucose concentration and urine production, the effect of general anesthesia on indices of renal function in clinically normal horses is likely of little consequence in most horses admitted for elective surgical procedures.     

Pharmacokinetics of meloxicam in plasma and urine of horses

OBJECTIVE: To determine pharmacokinetic parameters for meloxicam, a nonsteroidal anti-inflammatory drug, in horses. ANIMALS: 8 healthy horses. PROCEDURE: In the first phase of the study, horses were administered meloxicam once in accordance with a 2 x 2 crossover design (IV or PO drug administration; horses fed or not fed). The second phase used a multiple-dose regimen (daily oral administration of meloxicam for 14 days), with meloxicam administered at the recommended dosage (0.6 mg/kg). Plasma and urine concentrations of meloxicam were measured by use of validated methods with a limit of quantification of 10 ng/mL for plasma and 20 ng/mL for urine. RESULTS: Plasma clearance was low (mean +/- SD; 34 +/- 0.5 mL/kg/h), steady-state volume of distribution was limited (0.12 +/- 0.018 L/kg), and terminal half-life was 8.54 +/- 3.02 hours. After oral administration, bioavailability was nearly total regardless of feeding status (98 +/- 12% in fed horses and 85 +/- 19% in nonfed horses). During once-daily administration for 14 days, we did not detect drug accumulation in the plasma. Meloxicam was eliminated via the urine with a urine-to-plasma concentration that ranged from 13 to 18. Concentrations were detected for a relatively short period (3 days) after administration of the final daily dose. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study support once-daily administration of meloxicam regardless of the feeding status of a horse and suggest a period of at least 3 days before urine concentrations of meloxicam reach concentrations that could be used in drug control programs.     

Ventilation imaging in the horse with 99mtechnetium-DTPA radioaerosol

This study describes the development of a radioaerosol technique for horses using 99mtechnetium-DTPA (diethylenetriaminepentacetate). In 24 normal, adult horses, very satisfactory ventilation images were obtained with the technique. Four-minute administrations of the aerosol resulted in a mean uptake of radioactivity in the lung fields of 3.02 mCi, with mean maximum counts (+/- sd) of 159,800 +/- 75,000 per camera field. The mean clearance half-time for the 99mtechnetium-DTPA from the lung fields was 55.6 +/- 14.2 mins which is very similar to figures obtained for normal human and dog lungs. The results of this study suggest that ventilation imaging with 99mtechnetium-DTPA is a clinically practical method of obtaining regional information on ventilation function in the horse.     

Pharmacokinetics of fluconazole following intravenous and oral administration and body fluid concentrations of fluconazole following repeated oral dosing in horses

OBJECTIVE: To determine the pharmacokinetics of fluconazole in horses. ANIMALS: 6 clinically normal adult horses. PROCEDURE: Fluconazole (10 mg/kg of body weight) was administered intravenously or orally with 2 weeks between treatments. Plasma fluconazole concentrations were determined prior to and 10, 20, 30, 40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after administration. A long-term oral dosing regimen was designed in which all horses received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24 hours for 10 days. Fluconazole concentrations were determined in aqueous humor, plasma, CSF, synovial fluid, and urine after administration of the final dose. RESULTS: Mean (+/- SD) apparent volume of distribution of fluconazole at steady state was 1.21+/-0.01 L/kg. Systemic availability and time to maximum plasma concentration following oral administration were 101.24+/-27.50% and 1.97+/-1.68 hours, respectively. Maximum plasma concentrations and terminal half-lives after IV and oral administration were similar. Plasma, CSF, synovial fluid, aqueous humor, and urine concentrations of fluconazole after long-term oral administration of fluconazole were 30.50+/-23.88, 14.99+/-1.86, 14.19+/-5.07, 11.39+/-2.83, and 56.99+/-32.87 microg/ml, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Bioavailability of fluconazole was high after oral administration to horses. Long-term oral administration maintained plasma and body fluid concentrations of fluconazole above the mean inhibitory concentration (8.0 mg/ml) reported for fungal pathogens in horses. Fluconazole may be an appropriate agent for treatment of fungal infections in horses.     

Pharmacokinetic disposition of dimethyl sulfoxide administered intravenously to horses

Dimethyl sulfoxide (DMSO) was administered IV to 6 Thoroughbred horses at 2 dosages: 1.0 g/kg and 0.1 g/kg. The pharmacokinetics seemed linear, with biological half-lives of 8.6 +/- 0.3 hours and 9.8 +/- 2.2 hours for the 1.0 g/kg and 0.1 g/kg dosages, respectively. This was further substantiated by mean residence times of 9.8 +/- 0.44 hours and 13.8 +/- 4.25 hours, areas under the curve of 12.55 +/- 1.42 mg/ml/hr and 1.63 +/- 0.49 mg/ml/hr, and the clearances of 0.081 +/- 0.009 L/kg/hr and 0.066 +/- 0.022 L/kg/hr for the large and small dosages, respectively. At 12 hours after 1.0 g/kg was administered, 26.6% of the DMSO dose was excreted unchanged into the urine; at 12 hours after 0.1 g/kg was administered, 25.3% of the DMSO dose was excreted unchanged into the urine. It was predicted that 29.4% and 40.6% of the total DMSO dose would be excreted into the urine for the 1.0 g/kg and 0.1 g/kg dosages, respectively. A 10% DMSO concentration in normal saline solution was safe to give as rapid IV infusion. Slow administration is recommended for more concentrated solutions. Based on the half-life, DMSO should be administered 2 times a day IV for the treatment of increased intracranial pressure and/or cerebral edema in horses.     

Pharmacokinetics of acetazolimide after intravenous and oral administration in horses

OBJECTIVE: To determine the pharmacokinetics of acetazolamide administered IV and orally to horses. ANIMALS: 6 clinically normal adult horses. PROCEDURE: Horses received 2 doses of acetazolamide (4 mg/kg of body weight, IV; 8 mg/kg, PO), and blood samples were collected at regular intervals before and after administration. Samples were assayed for acetazolamide concentration by high-performance liquid chromatography, and concentration-time data were analyzed. RESULTS: After IV administration of acetazolamide, data analysis revealed a median mean residence time of 1.71 +/- 0.90 hours and median total body clearance of 263 +/- 38 ml/kg/h. Median steady-state volume of distribution was 433 +/- 218 ml/kg. After oral administration, mean peak plasma concentration was 1.90 +/- 1.09 microg/ml. Mean time to peak plasma concentration was 1.61 +/- 1.24 hours. Median oral bioavailability was 25 +/- 6%. CONCLUSIONS AND CLINICAL RELEVANCE: Oral pharmacokinetic disposition of acetazolamide in horses was characterized by rapid absorption, low bioavailability, and slower elimination than observed initially after IV administration. Pharmacokinetic data generated by this study should facilitate estimation of appropriate dosages for acetazolamide use in horses with hyperkalemic periodic paralysis.     

Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses

OBJECTIVE: To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. ANIMALS: 11 healthy adult horses. PROCEDURE: Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured. RESULTS: Mean +/- SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 +/- 0.37 microg/mL, 2.35 +/- 0.78 microg/mL, and 2.40 +/- 0.29 microg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean +/- SD voriconazole concentration in AH after a single orally administered dose was 0.86 +/- 0.22 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.     

Disposition of orally administered cefpodoxime proxetil in foals and adult horses and minimum inhibitory concentration of the drug against common bacterial pathogens of horses

OBJECTIVES: To determine the disposition of orally administered cefpodoxime proxetil in foals and adult horses and measure the minimum inhibitory concentrations (MICs) of the drug against common bacterial pathogens of horses. ANIMALS: 6 healthy adult horses and 6 healthy foals at 7 to 14 days of age and again at 3 to 4 months of age. PROCEDURE: A single dose of cefpodoxime proxetil oral suspension was administered (10 mg/kg) to each horse by use of a nasogastric tube. In 7- to 14-day-old foals, 5 additional doses were administered intragastrically at 12-hour intervals. The MIC of cefpodoxime for each of 173 bacterial isolates was determined by use of a commercially available test. RESULTS: In 7- to 14-day-old foals, mean +/- SD time to peak serum concentration (Tmax) was 1.7 +/- 0.7 hours, maximum serum concentration (Cmax) was 0.81 +/- 0.22 microg/mL, and elimination half-life (harmonic mean) was 7.2 hours. Disposition of cefpodoxime in 3- to 4-month-old foals was not significantly different from that of neonates. Adult horses had significantly higher Cmax and significantly lower Tmax, compared with values for foals. The MIC of cefpodoxime required to inhibit growth of 90% of isolates for Salmonella enterica, Escherichia coli, Pasteurella spp, Klebsiella spp, and beta-hemolytic streptococci was 0.38, 1.00, 0.16, 0.19, and 0.09 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration at a dosage of 10 mg/kg every 6 to 12 hours would appear appropriate for the treatment of equine neonates with bacterial infections.     

Detection and pharmacokinetics of salbutamol in thoroughbred racehorses following inhaled administration

Salbutamol sulphate (Ventolin Evohaler) was administrated via the inhalation route to six horses at a dose of 0.5 mg every 4 h during the day for 2 days (total dose 4 mg). Urine and blood samples were taken up to 92 h postadministration. Hydrolyzed plasma and urine were extracted using solid phase extraction (SPE). A sensitive tandem mass spectrometric method was developed in this study, achieving a lower limit of quantification (LLOQ) for salbutamol of 10 pg/mL in plasma and urine. The parent drug was identified using UPLC‐MS/MS. Most of the determined salbutamol plasma concentrations, post last administration, lie below the LLOQ of the method and so cannot be used for plasma PK analysis. Urine PK analysis suggests a half‐life consistent with the pharmacological effect duration. An estimate of the urine average concentration at steady‐state was collected by averaging the concentration measurements in the dosing period from ?12 to 0 h relative to the last administered dose. The value was averaged across the six horses and used to estimate an effective urine concentration as a marker of effective lung concentration. The value estimated was 9.6 ng/mL and from this a number of detection times were calculated using a range of safety factors.     

Clinical pharmacology and pharmacokinetics of flumequine after intravenous, intramuscular and oral administration in pigeons (Columba livid)

The in-vitro activity of flumequine against 157 strains of bacteria isolated from birds was determined. The minimum inhibitory concentration (MIC) of 96.3% of the Enterobacteriaceae, Proteus spp. and Yersinia pseudotuberculosis studied (n = 135) was less than or equal to 1 microgram/ml. Pharmacokinetics of flumequine in pigeons (Columba livia) was investigated after intravenous, intramuscular and oral administration. From the blood disappearance curves after i.v. bolus injection (10 mg/kg body weight) clearance rate, blood half-time and distribution volume were calculated. The recovery of unchanged flumequine from the droppings in 24 h was 37 +/- 10% of the administered dose. Flumequine was also given i.m. at two dose levels, 10 and 60 mg/kg body weight. The availability of flumequine as intact drug was 22 and 23%, respectively, in 24 h. Therapeutic blood levels were maintained for 4 and 10 h, respectively. After an oral dose of flumequine (60 mg/kg body weight) an availability of 6.7 +/- 2.5% and a peak blood concentration of 2.68 +/- 0.92 microgram/ml at 2 h after administration were found. The recovery of unchanged flumequine from the droppings in 24 h was 1.55 +/- 0.79% of the administered dose. With the exception of the i.m. dose of 10 mg/kg, all flumequine administrations made the pigeons vomit. It appears that blood concentrations below 3 micrograms/ml will not induce vomiting. On the basis of the present data, a dosage regimen for flumequine in pigeons of a priming dose of 30 mg/kg i.m., followed after 8 h by oral administration of 30 mg/kg, this dose being repeated every 8-12 h, would be expected to give blood concentrations between 1.44 and 2.88 micrograms/ml.     

Influence of furosemide treatment on fluid and electrolyte balance in horses

Alterations in electrolyte and acid-base balance were studied in 6 horses for 8 hours after furosemide administration (1 mg/kg of body weight, IM), and the results were compared with those for 5 healthy untreated horses (controls) kept under identical environmental conditions. In the treated group, decreases in plasma potassium, chloride, and calcium concentrations and increases in total plasma protein content persisted for the 8-hour observation period, whereas there was no change in plasma sodium concentration, osmolality, or packed cell volume. Plasma bicarbonate concentration and PCO2 remained high throughout the study, during which time venous blood pH was modestly increased only at the 6-hour sampling time. Furosemide treatment resulted in decreases in urine pH, specific gravity, osmolality, and potassium and calcium concentrations and increases in urine volume and total urine sodium, chloride, and calcium excretion. Body weight decreased 19.2 +/- 5.2 kg (mean +/- SD) in treated horses (4 +/- 1% of body weight), compared with a weight loss of 8 +/- 2.1 kg in untreated horses (1.5 +/- 0.4% of body weight) during the 8-hour experimental period. The increased fluid losses induced by the diuretic did not cause any obvious clinical signs in the horses. Pulse pressure, skin turgor, capillary refill time, and jugular distensibility remained unchanged throughout the experimental period.     

Bioavailability of oral penicillins in the horse: a comparison of pivampicillin and amoxicillin

The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 mg/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mg/kg. Ampicillin and amoxicillin concentrations in plasma, synovial fluid and urine were determined. Mean biological half-life of intravenously administered ampicillin and amoxicillin was 1.72 and 1.43 h respectively, whilst the distribution volume (Vss) appeared to be 0.180 and 0.192 1/kg. Orally administered pivampicillin and amoxicillin were rapidly absorbed. A maximum concentration in plasma of 3.80 micrograms/ml was reached 2 h after administration of pivampicillin to starved horses; in fed horses a maximum concentration of 5.12 micrograms/ml was reached 1 h after administration. After oral administration of amoxicillin a maximum concentration of 2.03 micrograms/ml was reached after 1 h. The (absolute) bioavailability of pivampicillin administered orally was 30.9% in starved horses and 35.9% in fed horses. The bioavailability of amoxicillin administered orally was 5.3% in starved horses.     

Pharmacokinetics of voriconazole following intravenous and oral administration and body fluid concentrations of voriconazole following repeated oral administration in horses

OBJECTIVE: To determine the pharmacokinetics of voriconazole following IV and PO administration and assess the distribution of voriconazole into body fluids following repeated PO administration in horses. ANIMALS: 6 clinically normal adult horses. PROCEDURES: All horses received voriconazole (10 mg/kg) IV and PO (2-week interval between treatments). Plasma voriconazole concentrations were determined prior to and at intervals following administration. Subsequently, voriconazole was administered PO (3 mg/kg) twice daily for 10 days to all horses; plasma, synovial fluid, CSF, urine, and preocular tear film concentrations of voriconazole were then assessed. RESULTS: Mean +/- SD volume of distribution at steady state was 1,604.9 +/- 406.4 mL/kg. Systemic bioavailability of voriconazole following PO administration was 95 +/- 19%; the highest plasma concentration of 6.1 +/- 1.4 microg/mL was attained at 0.6 to 2.3 hours. Mean peak plasma concentration was 2.57 microg/mL, and mean trough plasma concentration was 1.32 microg/mL. Mean plasma, CSF, synovial fluid, urine, and preocular tear film concentrations of voriconazole after long-term PO administration were 5.163 +/- 1.594 microg/mL, 2.508 +/- 1.616 microg/mL, 3.073 +/- 2.093 microg/mL, 4.422 +/- 0.8095 microg/mL, and 3.376 +/- 1.297 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole distributed quickly and widely in the body; following a single IV dose, initial plasma concentrations were high with a steady and early decrease in plasma concentration. Absorption of voriconazole after PO administration was excellent, compared with absorption after IV administration. Voriconazole appears to be another option for the treatment of fungal infections in horses.     

Gentamicin tissue concentrations in equine small intestine and large colon

Gentamicin sulfate (2.2 mg/kg of body weight, IV) was given to anesthetized horses. Jejunal and large colon tissue samples (1 g), serum, and urine were collected over a 4-hour period. Maximum gentamicin concentrations in serum (10.06 +/- 2.85 micrograms/ml) occurred at 0.25 hours after injection. Maximum gentamicin concentrations in the large colon (4.13 +/- 1.80 micrograms/ml) and jejunum (2.26 +/- 1.35 micrograms/ml) occurred in horses at 0.5 and 0.33 hours, respectively. Tissue concentrations decreased in parallel with serum concentrations and were still detectable at the end of the 4-hour period. During the time that samples were collected, the total amount of gentamicin excreted in the urine ranged from 7.21 +/- 3.11 mg to 11.91 +/- 7.12 mg, with a mean urinary concentration of 57.01 +/- 5.37 micrograms/ml. Over the 4-hour collection period, the fraction of dose that was excreted unchanged in the urine was 4.8 +/- 1.9%. Pharmacokinetic analyses of the serum concentration-time data gave a serum half-life of 2.52 +/- 1.29 hours, volume of distribution of 227 +/- 83 ml/kg, and body clearance of 1.12 +/- 0.26 ml/min/kg. The half-lives of the antibiotic in the jejunum and large colon were 1.32 and 1.33 hours, respectively.     

Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration

Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were determined in the obtained plasma samples by use of an LC/MS/MS method and were used for pharmacokinetic calculations. Tramadol clearance, apparent volume of distribution at steady-state, mean residence time (MRT) and half-life after intravenous administration were 26+/-3 mL/min/kg, 2.17+/-0.52 L/kg, 83+/-10 min, and 82+/-10 min, respectively. The MRT and half-life after intramuscular administration were 155+/-23 and 92+/-14 min. The mean absorption time was 72+/-22 min and the bioavailability 111+/-39%. Tramadol was poorly absorbed after oral administration and only 3% of the administered dose was found in systemic circulation. The fate of the tramadol M1 metabolite was also investigated. M1 appeared to be a minor metabolite in horses, which could hardly be detected in plasma samples. The poor bioavailability after oral administration and the short half-life of tramadol may restrict its usefulness in clinical applications.     

Comparison of standard and radionuclide methods for measurement of glomerular filtration rate and effective renal blood flow in female horses.

Comparison of standard and radionuclide methods for measuring glomerular filtration rate (GFR) and effective renal blood flow (ERBF) was performed in 8 healthy female horses. Inulin and p-aminohippurate solutions were administered IV as a bolus, followed by sustained administration. Urine and plasma inulin and p-aminohippurate concentrations and urine volume were measured. Glomerular filtration rate and ERBF were calculated on the basis of these measurements. Glomerular filtration rate and ERBF were measured on the basis of plasma clearance of the radiopharmaceuticals, 99mTc-labeled diethylene-triaminepentaacetic acid (99mTc-DTPA) and [131I]-o-iodohippuric acid (131I-OIH), respectively. Mean +/- SEM GFR, using inulin, was 1.83 +/- 0.21 ml/min/kg of body weight. Mean GFR, using 99mTc-DTPA was 1.79 +/- 0.18 ml/min/kg. Mean ERBF, using p-aminohippurate, was 15.13 +/- 1.28 ml/min/kg. Mean ERBF, using 131I-OIH, was 18.42 +/- 1.57 ml/min/kg. Analysis of variance indicated no significant difference between mean values for GFR and ERBF. Radionuclide measurement of GFR and ERBF compared well with standard methods and is an alternative technique to the cumbersome standard methods for determination of GFR and ERBF in horses.     

Phenylbutazone in the horse: a review

Phenylbutazone is an acidic, lipophilic, non-steroidal anti-inflammatory drug (NSAID). It is extensively metabolized in the horse. The metabolites so far identified, oxyphenbutazone, gamma-hydroxyoxyphenbutazone, account for some 25-30% of administered dose over 24 h. The plasma half-life of phenylbutazone and termination of its pharmacological action are determined primarily by its rate of hepatic metabolism. Phenylbutazone acts by inhibiting the cyclooxygenase enzyme system, which is responsible for synthesis of prostanoids such as PGE2. It appears to act on prostaglandin-H synthase and prostacyclin synthase, after conversion by prostaglandin-H synthase to reactive intermediates. It markedly reduces prostanoid-dependent swelling, edema, erythema, and hypersensitivity to pain in inflamed tissues. Its principal use in the horse is for treatment of soft tissue inflammation. Phenylbutazone is highly bound (greater than 98%) to plasma protein. After i.v. injection, blood levels decline with an elimination half-life of 3-10 h. The plasma kinetics of phenylbutazone may be dose dependent, with the plasma half-life increasing as the drug dosage level increases. Plasma residues of the drug at 24 h after a single i.v. dose of 2 g/450 kg average about 0.9 microgram/ml, but considerable variation occurs. If dosing is repeated, the plasma residue accumulates to give mean residual blood levels of approximately 4.5 microgram/ml on Day 5 after 4 days of dosing. Approximately similar blood levels are found after a combination of oral and i.v. dosing. Experiments on large numbers of horses in training have been undertaken to ascertain the population distributions of residual blood levels after such dosing schedules. Absorption of phenylbutazone from the gastrointestinal tract is influenced by the dose administered and the relationship of dosing to feeding. Access to hay can delay the time of peak plasma concentration to 18 h or longer. Under optimal conditions, the bioavailability of oral phenylbutazone is probably in the region of 70%. Paste preparations may be more slowly absorbed than other preparations and yield higher residual plasma levels at 24 h after dosing, but further controlled studies are required. Phenylbutazone is easily detected in the plasma and urine of horses but concentrations in saliva are low. It is quantitated for forensic purposes by HPLC. The variability of this method between laboratories is about +/- 25%. Increasing urinary pH increases the urinary concentration of phenylbutazone and its metabolites up to 200-fold.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of atracurium administered by continuous intravenous infusion in halothane-anesthetized horses

Atracurium (0.4 mg/ml in isotonic NaCl solution) was administered by IV infusion to 7 healthy adult horses for 2 hours. Over the 2-hour period, a 95 to 99% reduction of train-of-four hoof-twitch response was maintained by 0.17 +/- 0.01 mg of atracurium/kg of body weight/h, for a total of 161 +/- 6 mg of atracurium (mean +/- SEM) for horses 1 to 4, 6, and 7. Horse 5, a mare in estrus, required 0.49 mg of atracurium/kg/h to maintain comparable relaxation. Hoof-twitch recovery time from 10 to 75% of baseline strength was 19.8 +/- 2.5 minutes for all horses. The 10 to 75% recovery time for horse 5 was 18 minutes. Recovery time from discontinuation of halothane until standing was 86 +/- 14 minutes (range, 55 to 165 minutes). Horse 5 had a 165-minute recovery. Regarding recovery from anesthesia, 3 recoveries were rated as excellent, 1 recovery good, and 2 recoveries as fair. Horse 5 laid quietly until she stood with 1 strong, smooth effort.     

A pharmacokinetic study of phenobarbital in mature horses after oral dosing

The pharmacokinetics of phenobarbital were determined in six mature horses after a single oral dose. Horses were administered a 5.5 mg/kg of body weight oral dose of phenobarbital tablets. Based on the combined evaluation of i.v. and oral results, phenobarbital displayed two-compartment pharmacokinetics in the horse with a terminal half-life of 19.0 +/- 4.4 (mean +/- SD) h. This half-life is considerably shorter than those reported for dogs and humans. The steady-state volume of distribution (Vdss/F) and the total body clearance (Clt/F) of phenobarbital were 0.753 +/- 0.115 l/kg and 27.9 +/- 9.2 ml/h/kg, respectively. The average extent of oral absorption was 101% with a range of 76 to 124% among the six horses. Examination of the absorption kinetics demonstrated a biphasic absorption process in four horses with a rapid absorption followed by a slower absorption phase. The mean residence time (MRT) was 36.9 +/- 4.1 h and the mean residence time for oral absorption (MRTabs) was 11.3 h. Based on the results of the present study, an oral dosing regimen of 11 mg/kg of body weight every 24 h can be recommended.