Safety and effectiveness of cupric oxide particles for increasing liver copper stores in sheep

Five groups of four, housed Cheviot ewes (mean live-weight 50 kg) were given single doses of 0, 2.5, 5, 10 or 20 g cupric oxide particles in gelatin capsules while receiving a diet of marginal copper content based on pelleted oats. After 65 days liver copper concentrations had increased curvilinearly in relation to dose and all ewes given 10 or 20 g cupric oxide particles showed increases of at least 13.4 mmol kg-1 dry matter (850 ppm). Liver copper concentrations had generally declined after 85 days but biochemical and histological evidence of copper toxicity was recorded in one ewe which had received 20 g cupric oxide particles. Despite marked variations between individual sheep a dose of 0.1 g kg-1 liveweight (5 g) was considered to be safe and did not induce clinical copper toxicity in five sheep of the susceptible North Ronaldsay breed given the same basal diet.     

Copper oxide needles administered during early pregnancy improves the copper status of ewes and their lambs

AIM: To determine the effect of copper oxide (CuO) needles administered orally to ewes in early pregnancy on the copper (Cu) status of ewes throughout gestation and lactation, and of their lambs from birth to weaning. METHODS: In mid-April, after mating, 12 twin-bearing ewes were given an oral capsule containing 5 g CuO needles while 12 others served as untreated controls. Changes in Cu status were monitored by determining serum and liver Cu concentrations on Days 1, 62, 117, 153, 185 and 216 in the ewes, and at 1, 36, 68 and 99 days of age for lambs. Pasture herbage samples were collected at about 60-day intervals for Cu, molybdenum (Mo), iron (Fe) and sulphur (S) determinations. RESULTS: Copper status of the ewe flock was adequate, as initial mean serum and liver Cu concentrations were 15 micromol/L and 1,060 micromol/kg fresh tissue, respectively. The CuO needles did not affect serum Cu concentrations of the ewes or their lambs. Mean serum Cu concentration of all lambs at birth was about half that of ewes (8 vs 17 micromol/L), regardless of Cu supplementation, and not until at least 68 days of age was it similar to the dams'. Liver Cu concentrations of lambs at birth were also lower than that of the ewes (380 vs 640 micromol/kg fresh tissue among the controls), but changed little over time. CuO treatment increased liver Cu concentration in ewes for at least 185 days and in lambs for 36 days (p<0.05). Among untreated ewes, there was a seasonal decline in mean liver Cu concentrations, which were highest in autumn and lowest in early spring (1,060 vs 370 micromol/kg fresh tissue). The mean pasture mineral concentrations were Cu 5.7, Mo 0.48, Fe 194 and S 2,900 mg/kg dry matter (DM). CONCLUSIONS: CuO needles administered to ewes in early pregnancy increased their Cu status through gestation and early lactation, and the Cu status of their lambs for 36 days from birth. Serum Cu concentration was not affected by treatment but a marked rise was observed in all lambs between birth and 10 weeks of age. CLINICAL RELEVANCE: Copper deficiency in young lambs may be conveniently and effectively prevented by treating ewes with CuO needles during early pregnancy. The serum Cu concentration in lambs <8 weeks old may not reflect the Cu status of the flock.     

Safety and effectiveness of cupric oxide particles for increasing liver copper stores in cattle

Five groups of three or four crossbred steers, mean initial liveweight 220 kg, were given a diet of barley and hay ad libitum. Each animal received a single oral dose of 0, 5, 10, 20 or 40 g cupric oxide particles. A dose of 5 g cupric oxide particles increased liver copper stores for about 240 days and higher doses increased liver stores for longer but 40 g was no more effective than 20 g (85 mg kg-1 liveweight). Variation among individuals was marked but the highest liver copper concentration recorded (7.59 mmol kg-1 dry matter) produced no biochemical evidence of copper toxicity. Earlier, cupric oxide particles were separated into three fractions, clumps, short rods and long rods and 5 mg kg-1 liveweight of each fraction given to steers of 173 kg mean liveweight. The form of the particles did not affect either their retention in the alimentary tract or the accumulation of copper in the liver.     

Pharmacokinetics of an extended‐release formulation of eprinomectin in healthy adult alpacas and its use in alpacas confirmed with mange

The study objective was to determine the pharmacokinetics and clinical effects of an extended‐release 5% eprinomectin formulation (Longrange^®) following subcutaneous (s.c.) injection in healthy (n = 6) and mange‐infected (n = 4) adult alpacas. High‐performance liquid chromatography was used to analyze plasma samples obtained at regular intervals for 161 days following a single 5 mg/kg injection s.c. in healthy alpacas, and for 5 days following each dose (3 treatments, 2 months apart) in mange‐affected animals. Skin scrapings and biopsies were performed pre‐ and post‐treatment at two comparable sites in alpacas with mange. Four alpacas served as healthy controls. Eprinomectin plasma concentrations showed a biphasic peak (C_MAX‐1: 5.72 ± 3.25 ng/mL; C_MAX‐2: 6.06 ± 2.47 ng/mL) in all animals at 3.88 ± 5.16 days and 77 ± 12.52 days, respectively. Eprinomectin plasma concentrations remained above 1.27 ± 0.96 ng/mL for up to 120 days. Hematocrit (35.8 vs. 31.3%, P < 0.003) and albumin (3.5 vs. 2.8 g/dL P < 0.006) reduced significantly over 6 months in multidose animals, while fecal egg counts did not differ between groups. Self‐limiting injection site reactions occurred in 9 of 10 animals. Pre‐ and post‐treatment skin biopsies showed reduced hyperkeratosis, but increased fibrosis, with 1 of 4 alpacas remaining positive on skin scraping for mange. In conclusion, alpacas require a higher eprinomectin dose (5.0 mg/kg s.c.) than cattle, to reach comparable plasma concentrations.     

Copper oxide needles for cattle: a comparison with parenteral treatment

Two trials of oral copper oxide needles for cattle are described. In one, a dose of 13.0 g copper oxide/100 kg liveweight in yearling bullocks was compared with parenteral copper at a total dose rate of 400 mg copper. In the second, three oral dose rates (3.5, 7.0 and 10.5 g copper oxide/100 kg liveweight) in calves were compared over two years with a total dose of 500 mg parenteral copper. In both trials liver copper values reached a peak at about six weeks after oral dosing and in the second trial the peak was dose related. Thereafter liver levels declined in all the oral treatment groups; normal levels of more than 30 mg/kg liver dry matter were maintained for 30 weeks in the first trial and for 40 to 47 weeks, depending on dose rate, in the second. In both trials repeated parenteral treatments were required to maintain liver levels within the normal range. The results support earlier findings that an adequate dose of copper oxide needles can maintain the copper status of cattle for periods of at least six months.     

Pharmacokinetics of sulphanilamide and its three acetyl metabolites in dairy cows and calves

An intravenous low dosage of sulphanilamide (SAA) (14.0 mg/kg) to 6 pre-ruminant calves revealed a biphasic SAA plasma disposition with a mean elimination half-life of 4.1 h. The main metabolite in plasma was N4-acetylsulphanilamide (N4), which 4 hours after injection exceeded the parent SAA plasma concentration. Urinary recovery of SAA was 10 to 16% of the dose; of N4, it was at least 69%. Traces of the N1-acetyl (N1) metabolite and the doubly acetylated derivative (N1N4) were present in urine. The renal clearances of the N1 and N4 metabolites showed a tubular secretion pattern, which was at least 2 to 6 times higher than that of SAA. A single high oral SAA dose of 200 mg/kg to 3 dairy cows resulted in extensive metabolism of SAA into N4, N1, and N1N4 metabolites; their mean maximum plasma concentrations were 64, 48, 0.72 and 24 micrograms/ml, respectively. The mean disposition half-life of SAA in plasma and milk was 10 h. In milk the metabolite concentrations exceeded those in plasma; the N4 and N1N4 metabolite concentrations in milk exceeded that of SAA. The mean maximum concentrations of SAA, N4, N1, and N1N4 in milk were 52, 89, 2.3, and 98 micrograms/ml, respectively. For SAA and its metabolites, the binding to plasma and milk proteins was determined. No glucuronide or sulphate conjugates of SAA and its acetyl metabolites could be found in plasma, milk, or urine. Based on the sensitivity of the bioassay (0.2 micrograms SAA/ml), a withholding time of 5 days was suggested for milk following single oral SAA dosage of 200 mg/kg.     

Intramuscular and oral disposition of enrofloxacin in African grey parrots following single and multiple doses

The intramuscular (IM) and oral (PO) disposition of enrofloxacin, a new fluoroquinolone antimicrobial drug, were evaluated in African grey parrots. Peak enrofloxacin concentration, mean (+/- SEM), at 1 h following a 15-mg/kg IM dose was 3.87 (+/- 0.27) micrograms/ml and declined with a mean residence time of 3.05 h. Peak enrofloxacin plasma concentrations at 2 to 4 h following oral doses of 3, 15, and 30 mg/kg were 0.31 (+/- 0.11), 1.12 (+/- 0.11), and 1.69 (+/- 0.23) micrograms/ml, respectively, and declined with a mean residence time of 3.44-5.28 h. The relative bioavailability of the 15-mg/kg oral dose was 48%. An equipotent metabolite, ciprofloxacin, was detected in plasma at concentrations ranging from 3 to 78% of those of enrofloxacin. Enrofloxacin concentrations and area under the curve were significantly lower, the mean residence time significantly shorter and the ciprofloxacin/enrofloxacin ratios higher, following 10 days of oral treatment at 30 mg/kg every 12 h. Following 10 days of treatment, no significant biochemical changes were noted; however, polydipsia and polyuria occurred in treated birds, but resolved quickly upon discontinuation of enrofloxacin administration. These studies indicate that a rational starting dose for enrofloxacin in psittacines (7.5-30 mg/kg BID) should be higher than those in other domestic animals.     

Efficacy, distribution and faecal excretion of copper oxide wire particles in a novel bolus in red deer (Cervus elaphus)

AIM: To determine the efficacy of a novel copper oxide wire particle (COWP) formulation in elevating concentrations of copper (Cu) in the liver and serum of red deer (Cervus elaphus), and to investigate the distribution of particles in the gastrointestinal tract and the rate of their excretion in faeces. METHODS: Mixed-age red deer hinds were allocated to three groups (n=10 per group) on the basis of pre-treatment liver Cu concentrations. Groups 1 and 2 were treated orally with a 10-g COWP bolus on Days 0 and 30, respectively, while the remaining group served as an untreated control. Animals were slaughtered on Day 60, when blood and liver samples were collected for determination of Cu concentrations. An additional group of 18-month-old red deer hinds (n=20) were treated orally with a 10-g COWP bolus, and four were slaughtered on each of Days 1, 5, 15, 30 and 60 after treatment. The gastrointestinal tract was secured between compartments below the oesophagus and contents rinsed until sedimentation of particles was complete. The sediment was oven-dried and COWP were separated and weighed. Faeces were collected continuously from four additional animals held in metabolism cages for 4 days after treatment, sub-sampled daily, and COWP recovered. RESULTS: Mean liver Cu concentrations at slaughter were 80, 597 and 447 micromol/kg for controls and hinds treated 30, and 60 days previously, respectively. Corresponding mean serum Cu concentrations were 7.7, 12.9 and 11.9 micromol/L, respectively. Liver and serum Cu concentrations were higher in both treatment groups than in untreated control animals (p<0.001). COWP were found in all compartments of the gastrointestinal tract measured, for at least 15 days, and in the rumen/reticulum and abomasum for at least 60 days post-administration. The highest rate of recovery overall was from the rumen/reticulum. Mean weight of COWP recovered from faeces was 0.09 g during the first 24 h and 0.94 g over the first 4 days following administration. CONCLUSION: The COWP bolus tested resulted in elevated mean liver Cu concentrations for at least 60 days compared with control animals. The majority of COWP were found in the rumen/ reticulum, where recovery was possible for at least 60 days. About 10% of particle weight was excreted in the faeces within 4 days of administration. CLINICAL SIGNIFICANCE: The test bolus was efficacious in deer, elevating mean liver and serum Cu concentrations 30 and 60 days after treatment. Variation in faecal excretion may explain between-animal differences in efficacy.     

Pharmacokinetics of pipemidic acid in chickens after single intravenous and oral dosings

The pharmacokinetics of pipemidic acid after 2 single doses were studied in broiler chickens. Chickens were given single IV and oral doses of 10 and 30 mg of pipemidic acid/kg of body weight. Blood samples were collected over 8 hours after each dose administration. High-pressure liquid chromatography with UV detection was used to determine concentrations in plasma of pipemidic acid. The plasma concentration-time curves after IV administration followed 2-compartment characteristics, rapid initial distribution phase, and a terminal elimination phase. The pharmacokinetic variables differed significantly between single doses of 10 and 30 mg of pipemidic acid/kg. Mean disposition variables were a half-life at alpha phase of 0.06 hours or 0.33 hours, a half-life at beta phase of 1.18 hours or 1.72 hours, a volume of distribution in the central compartment of 0.12 L/kg or 0.31 L/kg, a volume of distribution during the elimination beta phase of 1.64 L/kg or 1.05 L/kg, and a total plasma clearance of 0.97 L/h.kg or 0.41 L/h.kg, for the 10 or 30 mg/kg dose, respectively. After oral administration, the pipemidic acid plasma profile could be adequately described by a 1-compartment model. After the single oral doses of 10 and 30 mg of pipemidic acid/kg, pipemidic acid was absorbed rapidly (time to maximal concentration of 0.31 hours or 0.71 hours) and eliminated with a mean half-life of 0.86 hours or 0.61 hours, respectively. The bioavailability was 39% at 10 mg of pipemidic acid/kg and 61% at 30 mg of pipemidic acid/kg.     

Pharmacokinetics of voriconazole after single dose intravenous and oral administration to alpacas

Voriconazole is a new antifungal drug that has shown effectiveness in treating serious fungal infections and has the potential for being used in large animal veterinary medicine. The objective of this study was to determine the plasma concentrations and pharmacokinetic parameters of voriconazole after single-dose intravenous (i.v.) and oral administration to alpacas. Four alpacas were treated with single 4 mg/kg i.v. and oral administrations of voriconazole. Plasma voriconazole concentrations were measured by a high-performance liquid chromatography method. The terminal half-lives following i.v. and oral administration were 8.01 ± 2.88 and 8.75 ± 4.31 h, respectively; observed maximum plasma concentrations were 5.93 ± 1.13 and 1.70 ± 2.71 μg/mL, respectively; and areas under the plasma concentration vs. time curve were 38.5 ± 11.1 and 9.48 ± 6.98 mg·h/L, respectively. The apparent systemic oral availability was low with a value of 22.7 ± 9.5%. The drug plasma concentrations remained above 0.1 μg/mL for at least 24 h after single i.v. dosing. The i.v. administration of 4 mg/kg/day voriconazole may be a safe and appropriate option for antifungal treatment of alpacas. Due to the low extent of absorption in alpacas, oral voriconazole doses of 20.4 to 33.9 mg/kg/day may be needed.     

Tolerance and pharmacokinetics of cephalexin in cats after oral administration

The tolerance of cephalexin in 10 cats was studied after oral administration of coated tablets (Cefaseptin; Chassot and Cie AG). Over a period of 21 days, the drug was administered twice daily at doses of 25, 30, 50 and 75 mg/kg body-weight. While the first three dose rates were well tolerated clinically, the highest dose was not. After seven days of treatment, signs of intolerance were salivation, vomiting and diarrhoea. Biochemical and haematological parameters (determined in blood, plasma and urine) were not altered. Plasma and skin concentrations of cephalexin were measured after oral treatment of cats with 25 and 50 mg cephalexin/kg body-weight. After treatment with 25 mg/kg body-weight, a mean elimination plasma half-life of 1–7 hours was calculated. The cephalexin concentration measured in the skin after two hours ranged from 8 to 22 per cent of the plasma level, so it is questionable if sufficiently high skin concentrations for efficacy are achieved with doses of 25 mg/kg body weight.     

Luteotrophic and luteolytic effects of nitric oxide in sheep are dose-dependent in vivo

It has been suggested that nitric oxide (NO) acts in either an anti-luteolytic or in a luteolytic manner, but the mechanism for these opposing roles is unclear. We hypothesized that NO may act in a dose-dependent manner to regulate luteal function, whereby low concentrations of NO might stimulate luteal progesterone production (i.e. luteotrophic) and high concentrations of NO might reduce concentrations of plasma progesterone (i.e. luteolytic). To test this hypothesis we infused increasing concentrations of the fast-acting NO donor, dipropylenetriamine NONOate (DPTA), into the arterial supply of sheep with ovarian transplants bearing a corpus luteum (CL). Infusions were performed on sheep with CL 11 days of age (n=9) or over 30 days of age (n=15). We measured changes in the concentration of progesterone in ovarian venous plasma during the 1-h infusion and for 24h after the infusion, and then compared the mean concentration of progesterone between treatment groups for effects by dose and dose by period interactions. Compared with saline-treated controls (n=6), the highest dose of 1000 microg/min DPTA (n=6) reduced (P0.05) in sheep infused with the lowest dose of 1 microg/min DPTA (n=6) compared with controls. We conclude that NO regulates luteal function in a dose-dependent manner in sheep in vivo.     

Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis)

Objective-To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Procedures-Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Results-Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Conclusions and Clinical Relevance-Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.     

Tissue distribution and disposition kinetics of enrofloxacin in healthy and E. coli infected broilers

Concentrations of enrofloxacin equivalent activity were determined by microbiological assay in the plasma of healthy and E. coli-infected broilers following single intravenous and oral administrations at 10 mg/kg. Tissue distribution and residue-depletion following multiple oral doses (10 mg/kg for 3 successive days) were investigated. Pharmacokinetic variables were determined using compartmental and non-compartmental analytical methods. Plasma enrofloxacin concentrations after intravenous dosing to healthy and infected birds were best described by a two-compartments model. Enrofloxacin concentrations in plasma of infected birds were lower than those of healthy ones. The disposition kinetics of intravenously administered drug in healthy and infected birds were somewhat different. The elimination half-life (t1/2 beta) was 4.75 vs. 3.63 h; mean residence time (MRT) was 6.72 vs 4.90 h; apparent volume of the central compartment (Vc) was 1.11 vs 1.57 l/kg; rate constant for transfer from peripheral to central compartment (k21) was 1.15 vs 1.41 h-1 and total body clearance (ClB) was 0.35 vs 0.53 l/h/kg in healthy and infected birds, respectively. After oral administration, the absorption half-life (t1/2abs) in the infected birds was significantly longer than in healthy birds, while elimination half-life (t1/2el) and MRT were significantly shorter. Bioavailability was higher in infected birds (72.50%) as compared to healthy ones (69.78%). Enrofloxacin was detected in the tissues of healthy and infected birds after daily oral dosing of 10 mg/kg for 3 days. It was more concentrated in liver, kidney, and breast muscle. The minimal inhibitory concentration (MIC) of enrofloxacin against E. coli was 0.064 microgram/ml. On the basis of maintaining enrofloxacin plasma concentrations over the MIC, a dose of 10 mg/kg given intravenously every 20.14 hrs or orally every 20.86 hrs should provide tissue concentrations effective against E. coli infection in chickens.     

Exenatide dosing in alpacas

In order to investigate whether exenatide could be used to stimulate glucose clearance and insulin secretion in alpacas without causing colic signs, six healthy adult alpacas were injected once a day with increasing subcutaneous doses. A follow‐up intravenous glucose injection was given to induce hyperglycemia, and serial blood samples were collected to measure plasma concentrations of glucose, insulin, triglycerides, beta‐hydroxybutyrate, and nonesterified fatty acids. The exenatide doses used were saline control (no drug), and 0.02, 0.05, or 0.1 mcg/kg injected subcutaneously. Alpacas had significantly lower plasma glucose concentrations and higher insulin concentrations on all treatment days compared with the control day, but the increase in insulin was significantly greater and lasted significantly longer when the alpacas received the two higher dosages. Two of the alpacas developed mild colic signs at the 0.05 mcg/kg dose and were not evaluated at the highest dose. Based on these findings, the 0.05 mcg/kg dose appears to offer the greatest stimulation of insulin secretion and glucose clearance without excessive risk or severity of complications.     

Pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole in alpacas

The pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole (TMP-SMX) were studied in six healthy male-castrate alpacas (Lama pacos) after intravenous (i.v.) or oral (p.o.) drug administration of 15 mg/kg TMP-SMX using a crossover design with a 2-week washout period. After 90 days one group (n = 3) was given a p.o. dose of 30 mg/kg TMP-SMX and the other group (n = 3) was given a p.o. dose of 60 mg/kg TMP-SMX. After i.v. administration of 15 mg/kg of TMP-SMX the mean initial plasma concentration (C0) was 10.75 +/- 2.12 microg/mL for trimethoprim (TMP) and 158.3 +/- 189.3 microg/mL for sulfamethoxazole (SMX). Elimination half-lives were 0.74 +/- 0.1 h for TMP and 2.2 +/- 0.6 h for SMX. The mean residence times were 1.45 +/- 0.72 h for TMP and 2.8 +/- 0.6 h for SMX. The areas under the respective concentration vs. time curves (AUC) were 2.49 +/- 1.62 microg h/mL for TMP and 124 +/- 60 microg h/mL for SMX. Total clearance (Clt) for TMP was 21.63 +/- 9.85 and 1.90 +/- 0.77 mL/min kg for SMX. The volume of distribution at steady state was 2.32 +/- 1.15 L/kg for TMP and 0.35 +/- 0.09 L/kg for SMX. After intragastric administration of 15, 30 and 60 mg/kg the peak concentration (Cmax) of SMX were 1.9 +/- 0.8, 2.6 +/- 0.4 and 2.8 +/- 0.7 microg/mL, respectively. The AUC was 9.1 +/- 5, 25.9 +/- 3.3 and 39.1 +/- 4.1 microg h/mL, respectively. Based upon these AUC values and correcting for dose, the respective bioavailabilities were 7.7, 10.5 and 7.94%. Trimethoprim was not detected in plasma after intragastric administration. These data demonstrate that therapeutic concentrations of TMP-SMX are not achieved after p.o. administration to alpacas.     

Pharmacokinetics of cimetidine in dogs after oral administration of cimetidine tablets

Long-term oral treatment with cimetidine is recommended to reduce vomiting in dogs with chronic gastritis. Despite this, few studies have specifically examined the plasma disposition and pharmacokinetics of cimetidine in dogs, particularly following repeated oral administration. The pharmacokinetics of cimetidine following oral administration as tablets was investigated in healthy dogs. Cimetidine was absorbed rapidly post-treatment ( t _max = 0.5 h). A mean absolute bioavailability of 75% was calculated following a single oral administration of 5 mg cimetidine/kg body weight. After intravenous administration, a plasma half-life of 1.6 h was calculated. Repeated oral administration at the recommended dose rate and regime (5 mg/kg body weight three times daily) for 30 consecutive days did not lead to any accumulation of cimetidine in plasma. Food intake concomitant with oral administration of cimetidine delayed ( t _max = 2.25 h) and decreased the rate and extent of absorption ( AUC ) by about 40%. Cimetidine was well absorbed in fasted dogs. Administration of food decreased the bioavailability of cimetidine by 40%. Cimetidine does not accumulate over time in plasma when administered long term to dogs.     

Pharmacokinetics and tissue concentrations of azithromycin in ball pythons (Python regius)

OBJECTIVE: To determine pharmacokinetics and tissue concentrations of azithromycin in ball pythons (Python regius) after IV or oral administration of a single dose. ANIMALS: 2 male and 5 female ball pythons. PROCEDURES: Using a crossover design, each snake was given a single dose of azithromycin (10 mg/kg) IV. After a 4-week washout period, each snake was given a single dose of azithromycin (10 mg/kg) orally. Blood samples were collected prior to dose administration and 1, 3, 6, 12, 24, 48, 72, and 96 hours after azithromycin administration. Azithromycin was quantitated by use of liquid chromatography-mass spectrometry. RESULTS: After IV administration, azithromycin had an apparent volume of distribution of 5.69 L/kg and a plasma clearance of 0.19 L/h/kg. Harmonic means for the terminal half-life were 17 hours following IV administration and 51 hours following oral administration. Mean residence times were 37 and 94 hours following IV and oral administration, respectively. Following oral administration, azithromycin had a peak plasma concentration (Cmax) of 1.04 microg/mL, a time to Cmax of 8.4 hours, and a prolonged mean absorption time of 57 hours. Mean oral bioavailability was 77%. Tissue concentrations ranged from 4 to 140 times the corresponding plasma concentration at 24 and 72 hours after azithromycin administration. CONCLUSIONS AND CLINICAL RELEVANCE: Azithromycin is well absorbed and tolerated by ball pythons. On the basis of plasma pharmacokinetics and tissue concentration data, we suggest an azithromycin dosage in ball pythons of 10 mg/kg, orally, every 2 to 7 days, depending upon the site of infection and susceptibil ity of the infective organism.     

Ketoconazole increases the plasma levels of ivermectin in sheep

The parasiticide ivermectin and the antifungal drug ketoconazole are drugs that interact with P-glycoprotein. We have tested the ability of ketoconazole at a clinical dose to modify the pharmacokinetics of ivermectin in sheep. Lacaune lambs were administered with a single oral dose of ivermectin alone at 0.2mg/kg (n=5) or in combination with a daily oral dose of ketoconazole (10mg/kg) given for 3 days before and 2 days after the ivermectin (n=5). The plasma kinetics of ivermectin and its metabolite were followed over 15 days by HPLC analysis. Co-administration of ketoconazole induced higher plasma concentrations of ivermectin, leading to a substantial increase in the overall exposure of the animals to the drug. Ketoconazole did not reduce the production of the main ivermectin metabolite but it may rather act by inhibiting P-glycoprotein, and thus increasing the absorption of ivermectin. The use of a P-gp reversing agent such as ketoconazole could be useful tool to optimize antiparasitic therapy in the face of the worldwide development of anthelmintic resistance.     

Measurement of cardiac troponin I utilizing a point of care analyzer in healthy alpacas

Background

Myocardial disease in camelids is poorly characterized. Nutritional (selenium deficiency) and toxic (ionophore toxicity) myocardial disease have been reported in camelids. Diagnosis and management of these and other myocardial diseases might be enhanced by evaluating cardiac troponin I (cTnI) concentrations. No information about cTnI reference intervals in camelids is currently available.

Hypothesis/Objectives

(A) To determine cTnI concentrations obtained using a point of care i-STAT^®1 analyzer (Heska Corporation) in healthy alpacas; (B) to compare alpaca cTnI concentrations between heparinized whole blood and plasma samples and between 2 different storage conditions (4 °C for 24 h or −80 °C for 30 days); (C) to examine assay reproducibility using the i-STAT^®1.

Animals, materials and methods

23 healthy alpacas were evaluated. Blood and plasma samples were analyzed by the i-STAT^®1 within 1 h of collection. Aliquots of plasma were stored at either 4 °C for 24 h or −80 °C for 30 days, and then analyzed. Assay reproducibility was determined by comparing 2 plasma or whole blood cTnI concentrations measured on the same sample over a 10 min period.

Results

Analyzer-specific plasma cTnI concentrations in clinically normal alpacas had a median of <0.02 ng/mL (range: <0.02 ng/mL to 0.07 ng/mL). Plasma and whole blood concentrations showed good agreement. Storage did not affect cTnI concentrations (p > 0.75). Plasma cTnI concentrations had coefficient of repeatability of 0.02 ng/mL.

Conclusions

The i-STAT^®1 can measure cTnI in alpacas on both plasma and whole blood and provides similar values for both samples. Storage at 4 °C for 24 h or −80 °C for 30 days does not affect estimates of plasma cTnI. Evaluation of cTnI might be of value in assessing cardiac disease in this species.