Pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar cells of foals

OBJECTIVE: To determine pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar (BAL) cells of foals. ANIMALS: 6 healthy 2-to 3-week-old foals. PROCEDURES: In a crossover design, clarithromycin (7.5 mg/kg) was administered to each foal via IV and intragastric (IG) routes. After the initial IG administration, 5 additional doses were administered IG at 12-hour intervals. Concentrations of clarithromycin and its 14-hydroxy metabolite were measured in serum by use of high-performance liquid chromatography. A microbiologic assay was used to measure clarithromycin activity in serum, urine, peritoneal fluid, synovial fluid, CSF, pulmonary epithelial lining fluid (PELF), and BAL cells. RESULTS: After IV administration, elimination half-life (5.4 hours) and mean +/- SD body clearance (1.27 +/- 0.25 L/h/kg) and apparent volume of distribution at steady state (10.4 +/- 2.1 L/kg) were determined for clarithromycin. The metabolite was detected in all 6 foals by 1 hour after clarithromycin administration. Oral bioavailability of clarithromycin was 57.3 +/- 12.0%. Maximum serum concentration of clarithromycin after multiple IG administrations was 0.88 +/- 0.19 microg/mL. After IG administration of multiple doses, clarithromycin concentrations in peritoneal fluid, CSF, and synovial fluid were similar to or lower than concentrations in serum, whereas concentrations in urine, PELF, and BAL cells were significantly higher than concentrations in serum. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of clarithromycin at 7.5 mg/kg every 12 hours maintains concentrations in serum, PELF, and BAL cells that are higher than the minimum inhibitory concentration (0.12 microg/mL) for Rhodococcus equiisolates for the entire 12-hour dosing interval.     

Quality Control of Compounded Crystalloid Fluids for Intravenous Delivery to Horses

Background

Periodic lack of availability and high cost of commercially produced isotonic fluids for intravenous (IV) use in horses have increasingly led to use of home‐made or commercially compound fluids by veterinarians. Data regarding the quality control and safety of compounded fluids would be of benefit to equine veterinarians.

Objectives

To compare electrolyte concentrations, sterility, and endotoxin contamination of commercially available fluids to 2 forms of compounded isotonic crystalloid fluids intended for IV use in horses.

Methods

Prospective study. Two methods of preparing compounded crystalloids formulated to replicate commercial Plasma‐Lyte A (Abbott, Chicago, IL) were compared. One formulation was prepared by a hand‐mixed method involving chlorinated drinking water commonly employed by equine practitioners, and the other was prepared by means of ingredients obtained from a commercial compounding pharmacy. The variables for comparison were electrolyte concentrations, sterility, and presence of endotoxin contamination.

Results

Electrolyte concentrations were consistent within each product but different between types of fluids (P < 0.0001). Hand‐mixed fluids had significantly more bacterial contamination compared to commercial Plasma‐Lyte A (P = 0.0014). One of the hand‐mixed fluid samples had detectable endotoxin contamination.

Conclusions and Clinical Importance

Chlorinated drinking water is not an acceptable source of water to compound isotonic fluids for IV administration. Equine practitioners should be aware of this risk and obtain the informed consent of their clients.     

Pharmacokinetics of tobramycin following intravenous,intramuscular, and intra‐articular administration in healthy horses

The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra‐articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3‐way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half‐life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be demonstrated to influence IV pharmacokinetics. The mean maximum plasma concentration (C_max) after IM administration was 18.24 ± 9.23 μg/mL at 1.0 h (range 1.0–2.0 h), with a mean bioavailability of 81.22 ± 44.05%. Intramuscular administration was well tolerated, despite the high volume of drug administered (50 mL per 500 kg horse). Trough concentrations at 24 h were below 2 μg/mL in all horses after all routes of administration. Specifically, trough concentrations at 24 h were 0.04 ± 0.01 μg/mL for the IV route, 0.04 ± 0.02 μg/mL for the IV/IA route, and 0.02 ± 0.02 for the IM route. An additional six mares received IA administration of 240 mg tobramycin. Synovial fluid concentrations were 3056.47 ± 1310.89 μg/mL at 30 min after administration, and they persisted for up to 48 h with concentrations of 14.80 ± 7.47 μg/mL. Tobramycin IA resulted in a mild chemical synovitis as evidenced by an increase in synovial fluid cell count and total protein, but appeared to be safe for administration. Monte Carlo simulations suggest that tobramycin would be effective against bacteria with a minimum inhibitory concentration (MIC) of 2 μg/mL for IV administration and 1 μg/mL for IM administration based on C_max:MIC of 10.     

Evaluation of the brain,renal, and hepatic effects of flunixin meglumine,ketoprofen, and phenylbutazone administration in Iranian fat-tailed sheep

Purpose  

The purpose of this study was to evaluate the brain, renal, and hepatic effects of three NSAIDs (flunixin meglumine, ketoprofen, and phenylbutazone) when administered IV to clinically normal Iranian fat-tailed sheep.     

Effect of Intravenous Administration of Cobalt Chloride to Horses on Clinical and Hemodynamic Variables

Background

Cobalt chloride (CoCl₂) is administered to racehorses to enhance performance. The purpose of this study was to evaluate the clinical, cardiovascular, and endocrine effects of parenterally administered CoCl₂.

Objectives

To describe the effects of weekly intravenous doses of CoCl₂ on Standardbred horses.

Animals

Five, healthy Standardbred mares.

Methods

Prospective, randomized, experimental dose‐escalation pilot. Five Standardbred mares were assigned to receive 1 of 5 doses of CoCl₂ (4, 2, 1, 0.5, or 0.25 mg/kg) weekly IV for 5 weeks. Physical examination, blood pressure, cardiac output, and electrocardiography (ECG) were evaluated for 4 hours after administration of the first and fifth doses. Blood and urine samples were collected for evaluation of cobalt concentration, CBC and clinical chemistry, and hormone concentrations.

Results

All mares displayed pawing, nostril flaring, muscle tremors, and straining after CoCl₂ infusion. Mares receiving 4, 2, or 1 mg/kg doses developed tachycardia after dosing (HR 60–126 bpm). Ventricular tachycardia was noted for 10 minutes after administration of the 4 mg/kg dose. Increases in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) occurred after administration of all doses (4, 2, 1, 0.5, and 0.25 mg/kg). Profound hypertension was observed after the 4 mg/kg dose (SAP/DAP, MAP [mmHg] = 291–300/163–213, 218–279). Hemodynamics normalized by 1–2 hours after administration. ACTH and cortisol concentrations increased within 30 minutes of administration of all CoCl₂ doses, and cardiac troponin I concentration increased after administration of the 4 and 2 mg/kg doses.

Conclusions and Clinical Importance

The degree of hypertension and arrhythmia observed after IV CoCl₂ administration raises animal welfare and human safety concerns.     

Pharmacokinetics of danofloxacin and N‐desmethyldanofloxacin in adult horses and their concentration in synovial fluid

The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N‐desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N‐desmethyldanofloxacin were measured by UPLC‐MS/MS. After i.v. administration, danofloxacin had an apparent volume of distribution (mean ± SD) of 3.57 ± 0.26 L/kg, a systemic clearance of 357.6 ± 61.0 mL/h/kg, and an elimination half‐life of 8.00 ± 0.48 h. Maximum plasma concentration (C_max) of N‐desmethyldanofloxacin (0.151 ± 0.038 μg/mL) was achieved within 5 min of i.v. administration. Peak danofloxacin concentrations were significantly higher after i.m. (1.37 ± 0.13 μg/mL) than after IG administration (0.99 ± 0.1 μg/mL). Bioavailability was significantly higher after i.m. (100.0 ± 12.5%) than after IG (35.8 ± 8.5%) administration. Concentrations of danofloxacin in synovial fluid samples collected 1.5 h after administration were significantly higher after i.v. (1.02 ± 0.50 μg/mL) and i.m. (0.70 ± 0.35 μg/mL) than after IG (0.20 ± 0.12 μg/mL) administration. Monte Carlo simulations indicated that danofloxacin would be predicted to be effective against bacteria with a minimum inhibitory concentration (MIC) ≤0.25 μg/mL for i.v. and i.m. administration and 0.12 μg/mL for oral administration to maintain an area under the curve:MIC ratio ≥50.     

Disposition of ampicillin trihydrate in plasma,uterine tissue,lochial fluid,and milk of postpartum dairy cattle

The objective of this study was to determine the disposition of ampicillin in plasma, uterine tissue, lochial fluid, and milk of postpartum dairy cattle. Ampicillin trihydrate was administered by intramuscular (i.m.) injection at a dose of 11 mg/kg of body weight every 24 h (n = 6, total of 3 doses) or every 12 h (n = 6, total of 5 doses) for 3 days. Concentrations of ampicillin were measured in plasma, uterine tissue, lochial fluid, and milk using HPLC with ultraviolet absorption. Quantifiable ampicillin concentrations were found in plasma, milk, and lochial fluid of all cattle within 30 min, 4 h, and 4 h of administration of ampicillin trihydrate, respectively. There was no significant effect of dosing interval (every 12 vs. every 24 h) and no significant interactions between dosing interval and sampling site on the pharmacokinetic variable measured or calculated. Median peak ampicillin concentration at steady‐state was significantly higher in lochial fluid (5.27 μg/mL after q 24 h dosing) than other body fluids or tissues and significantly higher in plasma (3.11 μg/mL) compared to milk (0.49 μg/mL) or endometrial tissue (1.55 μg/mL). Ampicillin trihydrate administered once daily by the i.m. route at the label dose of 11 mg/kg of body weight achieves therapeutic concentrations in the milk, lochial fluid, and endometrial tissue of healthy postpartum dairy cattle.     

Pharmacokinetics of the opioid antagonist N-methylnaltrexone and evaluation of its effects on gastrointestinal tract function in horses treated or not treated with morphine

OBJECTIVE: To determine the pharmacokinetics and effects of the morphine antagonist N-methylnaltrexone (MNTX) on gastrointestinal tract function in horses when administered alone and in combination with morphine. ANIMALS: 5 healthy adult horses. PROCEDURES: Horses were treated with MNTX (1 mg/kg, IV), and serial blood samples were collected for determination of drug pharmacokinetics. For evaluation of effects on the gastrointestinal tract when administered alone, MNTX was administered at a dosage of 0.75 mg/kg, IV, twice daily for 4 days. For evaluation of effects when administered concurrently with morphine, MNTX (0.75 mg/kg, IV, q 12 hours) and morphine (0.5 mg/kg, IV, q 12 hours) were administered for 6 days. Gastrointestinal variables evaluated were defecation frequency, weight of feces produced, fecal moisture content, intestinal transit time, and borborygmus scores. RESULTS: The time-concentration data for MNTX disposition best fit a 2-compartment model with a steady-state volume of distribution of 244.6 +/- 21.8 mL/kg, t1/2 of 47.04 +/- 11.65 minutes, and clearance of 11.43 +/- 1.06 mL/min/kg. Adverse effects were not observed at doses 相似文献   

Pharmacokinetics of cyclophosphamide after oral and intravenous administration to dogs with lymphoma

Background: Cyclophosphamide is an alkylating chemotherapeutic drug administered IV or PO. It is currently assumed that exposure to the active metabolite, 4‐hydroxycyclophosphamide (4‐OHCP), is the same with either route of administration.

Objectives:

To characterize the pharmacokinetics of cyclophosphamide and 4‐OHCP in dogs with lymphoma when administered PO or IV. Animals: Sixteen client‐owned dogs with substage A lymphoma were enrolled in the study. Eight dogs received cyclophosphamide IV and 8 received it PO. Methods: Prospective randomized clinical trial was performed. Blood was collected from each dog at specific time points after administration of cyclophosphamide. The serum was evaluated for the concentration of cyclophosphamide and 4‐OHCP with mass spectrometry and liquid chromatography. Results: Drug exposure to cyclophosphamide measured by area under the curve (AUC)_0–inf is significantly higher after intravenous administration (7.14 ± 3.77 μg/h/mL) compared with exposure after oral administration (P‐value < .05). No difference in drug exposure to 4‐OHCP was detected after IV (1.66 ± 0.36 μg/h/mL) or PO (1.42 ± 0.64 μg/h/mL) administered cyclophosphamide. Conclusions and Clinical Importance: Drug exposure to the active metabolite 4‐OHCP is equivalent after administration of cyclophosphamide either PO or IV.     

Furosemide continuous rate infusion diluted with 5% dextrose in water or hypertonic saline in normal adult dogs: a pilot study

Objective

The goal of this study was to investigate the short-term safety and diuretic efficacy of furosemide constant rate infusion (CRI) diluted with 5% dextrose in water (D5W) compared to dilution with 2.4% hypertonic saline in healthy dogs.

Pharmacokinetics and plasma concentrations of acetylsalicylic acid after intravenous, rectal, and intragastric administration to horses

Six healthy adult horses (5 mares and 1 stallion) were given a single dose of acetylsalicylic acid (ASA), 20 mg/kg of body weight, by intravenous (IV), rectal, and intragastric (IG) routes. Serial blood samples were collected via jugular venipuncture over a 36-h period, and plasma ASA and salicylic acid (SA) concentrations were determined by high-performance liquid chromatography. After IV administration, the mean elimination rate constant of ASA (± the standard error of the mean) was 1.32 ± 0.09 h⁻l, the mean elimination half-life was 0.53 ± 0.04 h, the area under the plasma concentration-versus-time curve (AUC) was 2555 ± 98 μg · min/mL, the plasma clearance was 472 ± 18.9 mL/h/kg, and the volume of distribution at steady state was 0.22 ± 0.01 L/kg. After rectal administration, the plasma concentration of ASA peaked at 5.05 ± 0.80 μg/mL at 0.33 h, then decreased to undetectable levels by 4 h; the plasma concentration of SA peaked at 17.39 ± 5.46 μg/mL at 2 h, then decreased to 1.92 ± 0.25 μg/mL by 36 h. After rectal administration, the AUC for ASA was 439.4 ± 94.55 μg · min/mL and the bioavailability was 0.17 ± 0.037. After IG administration, the plasma concentration of ASA peaked at 1.26 ± 0.10 μg/mL at 0.67 h, then declined to 0.37 ± 0.37 μg/mL by 36 h; the plasma concentration of SA peaked at 23.90 ± 4.94 μg/mL at 4 h and decreased to 0.85 ± 0.31 μg/mL by 36 h. After IG administration, the AUC for ASA was 146.70 ± 24.90 μg · min/mL and the bioavailability was 0.059 ± 0.013. Administration of a single rectal dose of ASA of 20 mg/kg to horses results in higher peak plasma ASA concentrations and greater bioavailability than the same dose given IG. Plasma ASA concentrations after rectal administration should be sufficient to inhibit platelet thromboxane production, and doses lower than those suggested for IG administration may be adequate.     

Renal Replacement Therapy in Healthy Adult Horses

Background

Renal replacement therapy (RRT) has been implemented extensively in people to facilitate recovery from acute renal failure (ARF). RRT has not been explored in horses, but might provide a further treatment option in horses with ARF.

Objective

To investigate efficacy and safety of RRT in horses.

Animals

Five healthy adult horses.

Methods

A prospective study was performed on horses restrained in stocks and intravenously connected to a commercial RRT machine to allow continuous venovenous hemodiafiltration to be performed for 6 hours. The RRT machine was set at the following flow rates: blood flow rate 250 mL/min; dialysate rate 3,000 mL/h; prefilter replacement pump 3,000 mL/h; and postfilter replacement pump rate 2,000 mL/h. Balanced electrolyte solution was used as dialysate and replacement fluid. Heart rate, respiratory rate, body temperature, direct arterial blood pressure, urine output, and various clinicopathologic parameters were measured over the study period.

Results

Renal replacement therapy was successfully performed in horses, resulting in a mean creatinine clearance of 0.127 mL/kg/min (68.9 mL/min) and urea reduction ratio of 24%. No adverse effects were detected although a significant decrease in rectal temperature was observed (P ≤ .007). A significant increase in serum phosphorus (P ≤ .001) and decrease in BUN (P < .001) were also noted. A significant prolongation of prothrombin (P < .01) and partial thromboplastin time (P < .0001) were observed along with a decrease in platelet count (P ≤ .04).

Conclusions and Clinical Importance

Renal replacement therapy can safely and effectively be used in adult horses.     

Comparative pharmacokinetics of minocycline in foals and adult horses

The objective of this study was to compare the pharmacokinetics of minocycline in foals vs. adult horses. Minocycline was administered to six healthy 6‐ to 9‐week‐old foals and six adult horses at a dose of 4 mg/kg intragastrically (IG) and 2 mg/kg intravenously (i.v.) in a cross‐over design. Five additional oral doses were administered at 12‐h intervals in foals. A microbiologic assay was used to measure minocycline concentration in plasma, urine, synovial fluid, and cerebrospinal fluid (CSF). Liquid chromatography–tandem mass spectrometry was used to measure minocycline concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar (BAL) cells. After i.v. administration to foals, minocycline had a mean (±SD) elimination half‐life of 8.5 ± 2.1 h, a systemic clearance of 113.3 ± 26.1 mL/h/kg, and an apparent volume of distribution of 1.24 ± 0.19 L/kg. Pharmacokinetic variables determined after i.v. administration to adult horses were not significantly different from those determined in foals. Bioavailability was significantly higher in foals (57.8 ± 19.3%) than in adult horses (32.0 ± 18.0%). Minocycline concentrations in PELF were higher than in other body fluids. Oral minocycline dosed at 4 mg/kg every 12 h might be adequate for the treatment of susceptible bacterial infections in foals.     

Effect of N‐Acetylcysteine Supplementation on Intracellular Glutathione,Urine Isoprostanes,Clinical Score,and Survival in Hospitalized Ill Dogs

Background

Antioxidant depletion and lipid peroxidation have been correlated with disease severity and associated with poor outcomes.

Hypothesis/Objectives

Supplementing dogs with N‐acetylcysteine (NAC) during the first 48 hours of hospitalization will increase cysteine, normalize glutathione concentrations, and decrease the degree of lipid peroxidation associated with illness.

Animals

Sixty systemically ill hospitalized client‐owned dogs and 14 healthy control dogs.

Methods

Randomized investigator‐blinded, placebo‐controlled prospective study. Dogs were randomized to treatment with NAC (n = 30) versus placebo (n = 30). Antioxidants, urine 8‐isoprostane/creatinine (IP/Cr), and clinical score were determined before and after treatment with NAC. Glutathione, cysteine, and vitamin E concentrations were quantified using high‐performance liquid chromatography. Atomic absorption spectroscopy and enzyme‐linked immunosorbent assays were used to quantify selenium and isoprostane concentrations, respectively.

Results

Ill dogs had significantly lower vitamin E concentrations (27 versus 55 μg/mL; P = .0005) as well as elevated IP/Cr ratios (872 versus 399 pg/mg; P = .0007) versus healthy dogs. NAC supplementation significantly increased plasma cysteine (8.67 versus 15.1 μM; P < .0001) while maintaining glutathione concentrations. Dogs in the placebo group experienced a statistically significant decrease in glutathione concentrations (1.49 versus 1.44 mM; P = .0463). Illness severity and survival were unchanged after short duration NAC supplementation.

Conclusions

Ill dogs experience systemic oxidative stress. Supplementation with NAC during the first 48 hours of hospitalization stabilized erythrocyte glutathione concentrations. The clinical impact of this supplementation and glutathione concentration stabilization was undetermined.     

Hemodynamic and Biochemical Alterations in Dogs with Lymphoma after Induction of Chemotherapy

Background

Doxorubicin is a common antineoplastic agent with dose‐dependent cardiotoxic adverse effects, and pre‐existing myocardial dysfunction is a contraindication to its use.

Objectives

To systematically define the hemodynamic and biochemical alterations in dogs undergoing chemotherapy for newly diagnosed lymphoma and assess the reversibility of these alterations with fluid administration.

Animals

Twenty‐one client‐owned dogs with newly diagnosed lymphoma were evaluated 1 week after induction of chemotherapy. Underlying degenerative valve disease was exclusionary. Eighteen healthy age‐ and weight‐matched dogs were used as controls.

Methods

Physical examination, blood pressure by Doppler, echocardiography, and biochemical evaluation (routine serum biochemistry, plasma renin activity and aldosterone concentrations, plasma and urine osmolalities, and urine electrolyte concentrations) were measured in dogs with lymphoma and compared to controls. Dogs with lymphoma received crystalloids IV at 6 mL/kg/h for 24 hours. All variables were reassessed at 4 and 24 hours. Deuterium oxide dilution and bromide dilution were used to determine total body water and extracellular water space, respectively.

Results

Baseline echocardiograms showed significantly smaller chamber dimensions in dogs with lymphoma compared to controls. These changes were reversed by fluid administration. Systolic blood pressure and urine sodium concentration were significantly increased, and bromide dilution space, PCV, urine specific gravity, and urine potassium concentration were significantly decreased compared to controls.

Conclusion and Clinical Importance

Echocardiographic and biochemical abnormalities in dogs with lymphoma appear consistent with volume depletion, and may be the result of systemic hypertension and subsequent pressure natriuresis.     

Pharmacokinetics of intra‐articular betamethasone sodium phosphate and betamethasone acetate and endogenous hydrocortisone suppression in exercising horses

To the date, no reports exist of the pharmacokinetics (PK) of betamethasone (BTM) sodium phosphate and betamethasone acetate administered intra‐articular (IA) into multiple joints in exercising horses. The purpose of the study was to determine the PK of BTM and HYD concentrations in plasma and urine after IA administration of a total of 30 mg BTM. Eight 4 years old Thoroughbred mares were exercised on a treadmill and BTM was administered IA. Plasma and urine BTM and HYD were determined via high performance liquid chromatography spectrometry for 6 weeks. Concentration‐time profiles of BTM and HYD in plasma and urine were used to generate PK estimates for non‐compartmental analyses and comparisons among times and HYD concentrations. BTM in plasma had greater T_max (T_max 0.8 h) vs. urine (T_max 7.1 h). Urine BTM concentration (ng/mL) and amount (AUC_last; h × ng/mL) were greater than plasma. HYD was suppressed for at least 3 days (<1 ng/mL) for all horses. The time of last quantifiable concentration of BTM (T_last; hour) was not significantly different in plasma than urine. Use of highly sensitive HPLC‐MS/MS assays enabled early detection and prolonged and consistent determination of BTM in plasma and urine.     

Pharmacokinetics of metronidazole in foals: influence of age within the neonatal period

Neonatal foals have unique pharmacokinetics, which may lead to accumulation of certain drugs when adult horse dosage regimens are used. Given its lipophilic nature and requirement for hepatic metabolism, metronidazole may be one of these drugs. The purpose of this study was to determine the pharmacokinetic profiles of metronidazole in twelve healthy foals at 1–2.5 days of age when administered as a single intravenous (IV) and intragastric (IG) dose of 15 mg/kg. Foals in the intravenous group were studied a second time at 10–12 days of age to evaluate the influence of age on pharmacokinetics within the neonatal period. Blood samples were collected at serial time points after metronidazole administration. Metronidazole concentration in plasma was measured using LC‐MS. Pharmacokinetic parameters were determined using noncompartmental analysis and compared between age groups. At 1–2.5 days of age, the mean peak plasma concentration after IV infusion was 18.79 ± 1.46 μg/mL, elimination half‐life was 11.8 ± 1.77 h, clearance was 0.84 ± 0.13 mL/min/kg and the volume of distribution (steady‐state) was 0.87 ± 0.07 L/kg. At 10–12 days of age, the mean peak plasma concentration after IV infusion was 18.17 ± 1.42 μg/mL, elimination half‐life was 9.07 ± 2.84 h, clearance was 1.14 ± 0.21 mL/min/kg and the volume of distribution (steady‐state) was 0.88 ± 0.06 L/kg. Oral approximated bioavailability was 100%. Cmax and T_max after oral dosing were 14.85 ± 0.54 μg/mL and 1.75 (1–4) h, respectively. The elimination half‐life was longer and clearance was reduced in neonatal foals at 1–2.5 days as compared to 10–12 days of age (P = 0.006, P = 0.001, respectively). This study warrants consideration for altered dosing recommendations in foals, especially a longer interval (12 h).     

Body fluid concentrations and pharmacokinetics of chloramphenicol given to mares intravenously or by repeated gavage

Serum concentrations and the pharmacokinetics of chloramphenicol were determined in 6 healthy mares after a single IV administration (50 mg/kg of body weight) or after the 1st and 5th sequential intragastric (IG) administration (50 mg/kg/6 hours) of chloramphenicol. Synovial fluid, peritoneal fluid, CSF, and urinary concentrations of chloramphenicol after the IG administrations also were determined. Mean (+/- SEM) overall elimination rate constant (K) values for the IV, 1st IG, and 5th IG dosages were 0.42 +/- 0.064/hr, 0.42 +/- 0.049/hr, and 0.29 +/- 0.074/hr, respectively, and were not significantly different from one another (P greater than 0.05). Bioavailability was 40 +/- 8.6% after the 1st IG administration and was 21 +/- 5.2% after the 5th IG administration. Values for the area under the curve (AUC) for the 1st and 5th IG dosages were significantly different from the AUC value for the IV dosage, and the AUC value for the 5th IG dosage was significantly different from that for the 1st IG dosage. Chloramphenicol was administered to 2 mares in 6 consecutive doses; the first and last doses were given IV and the others were given IG. Mean K values after the 2 IV doses were 0.38 +/- 0.112/hr and 0.56 +/- 0.078/hr, which were not significantly different from each other or from the mean value for the IV dosage given to all 6 mares. Absorption of chloramphenicol decreased with repeated IG administrations, resulting in lower concentrations of chloramphenicol with subsequent administrations. Five consecutive IG doses of chloramphenicol were administered to 4 of the mares in a separate experiment and did not alter intestinal xylose absorption.     

Effects of 6% Tetrastarch and Lactated Ringer's Solution on Extravascular Lung Water and Markers of Acute Renal Injury in Hemorrhaged,Isoflurane‐Anesthetized Healthy Dogs

Background

Tetrastarch can cause acute kidney injury (AKI) in humans with sepsis, but less likely to result in tissue edema than lactated Ringer's solution (LRS).

Objectives

Compare effects of volume replacement (VR) with LRS and 6% tetrastarch solution (TS) on extravascular lung water (EVLW) and markers of AKI in hemorrhaged dogs.

Animals

Six healthy English Pointer dogs (19.7–35.3 kg).

Methods

Prospective crossover study. Animals underwent anesthesia without hemorrhage (Control). Two weeks later, dogs hemorrhaged under anesthesia on 2 occasions (8‐week washout intervals) and randomly received VR with LRS or TS at 3 : 1 or 1 : 1 of shed blood, respectively. Anesthesia was maintained until 4 hour after VR for EVLW measurements derived from transpulmonary thermodilution cardiac output. Neutrophil gelatinase‐associated lipocalin (NGAL) and creatinine concentrations in plasma and urine were measured until 72 hour after VR.

Results

The EVLW index (mL/kg) was lower at 1 hour after TS (10.0 ± 1.9) in comparison with controls (11.9 ± 3.4, P = 0.04), and at 4 hour after TS (9.7 ± 1.9) in comparison with LRS (11.8 ± 2.7, P = 0.03). Arterial oxygen partial pressure‐to‐inspired oxygen fraction ratio did not differ among treatments from 0.5 to 4 hour after VR. Urine NGAL/creatinine ratio did not differ among treatments and remained below threshold for AKI (120,000 pg/mg).

Conclusions and Clinical Importance

Although TS causes less EVLW accumulation than LRS, neither fluid produced evidence of lung edema (impaired oxygenation). Both fluids appear not to cause AKI when used for VR after hemorrhage in healthy nonseptic dogs.