Oxytetracycline Pharmacokinetics in Rainbow Trout during and after an Orally Administered Medicated Feed Regimen

Abstract

The pharmacokinetic–pharmacodynamic predictor of antimicrobial activity for tetracyclines is reported to be the area under the concentration–time curve at steady state (AUC_ss) divided by the minimal inhibitory concentration of the targeted pathogen. Here, we estimate AUC_ss values for oxytetracycline (OTC) in serum of rainbow trout Oncorhynchus mykiss by using a destructive sampling study design. Seventy-two rainbow trout were fed OTC-medicated feed at 74.7 ± 1.5 mg/kg (mean ± SD) body weight (BW) by oral gavage for 10 consecutive days. Serum was collected from nine fish at 1, 3, 6, 8, 10, 12, 15, and 22 d after dosing began. Serum OTC concentrations were measured by high-performance liquid chromatography with a 0.01-μg/mL limit of detection. The average OTC AUC_ss was 29.2 μg × h/mL and was estimated using nonlinear mixed-effects modeling and bootstrap resampling techniques. The elimination half-life was estimated as 85.0 h, and the fraction of steady state achieved was estimated as 0.85. The calculated AUC_ss (24.8 μg × h/mL) following 10 d of oral dosing with 75 mg OTC/kg BW was less than the estimated AUC_ss. Results suggest that the pharmacokinetics of OTC exposure, including the AUC_ss, is better evaluated by using multiday dosimetry than by using a standard single-dose protocol.

Received September 29, 2011; accepted January 30, 2012     

Risk factors for superficial digital flexor tendinopathy in Thoroughbred racehorses in steeplechase starts in the United Kingdom (2001–2009)

The objective of this study was to identify risk factors for superficial digital flexor (SDF) tendinopathy in Thoroughbred horses in steeplechase races in the United Kingdom. Potential risk factors for SDF tendinopathy were studied between 1st January 2001 and 31st December 2009 using a cohort study design with 648 injuries sustained in 102,894 starts. Potential risk factors were screened using univariable logistic regression prior to multivariable model building.In the final multivariable model, 12 statistically significant risk factors were identified. Variables that increased the odds of SDF tendinopathy included firmer going, increased horse age, and racing in the summer compared to other seasons. Variables that decreased the odds included having a higher official rating and the number of starts in the preceding days.Fewer and different risk factors were identified than in an equivalent model of SDF tendinopathy in hurdle racing, highlighting potential differences between these disciplines. Further collection of training and racecourse information would be beneficial and may help to explain further some of the associations identified in this study. The results will facilitate the development of strategies to improve overall safety of horses in UK steeplechase racing.     

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin after Intramuscular Administration of Enrofloxacin in Goats

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats after a single intramuscular administration of enrofloxacin at 2.5 mg/kg body weight. The plasma concentrations of enrofloxacin and ciprofloxacin were determined simultaneously by a HPLC method. The peak concentrations (C _max) of enrofloxacin (1.13 g/ml) and ciprofloxacin (0.24 g/ml) were observed at 0.8 and 1.2 h, respectively. The elimination half-life (t _1/2), volume of distribution (V _d(area)), total body clearance (Cl_B) and mean residence time (MRT) of enrofloxacin were 0.74 h, 1.42 L/kg, 1329 ml/h per kg and 1.54 h, respectively. The t _1/2, area under the plasma concentration–time curve (AUC) and the MRT of ciprofloxacin were 1.38 h, 0.74 g h/ml and 2.73 h, respectively. The metabolic conversion of enrofloxacin to ciprofloxacin was appreciable (36%) and the sum of the plasma concentrations of enrofloxacin and ciprofloxacin was maintained at or above 0.1 g/ml for up to 4 h. Enrofloxacin appears to be useful for the treatment of goat diseases associated with pathogens sensitive to this drug.     

Variance estimation for population attributable risk in a complex cross-sectional animal health survey

Population attributable risk estimates offer a method of combining information on population exposure and disease risk factors into a single measure. Univariate and multivariable methods exist for calculating point estimates and variances under the assumption of equal sampling probabilities. National Animal Health Monitoring System national studies typically use a complex survey design (where selection probabilities vary by design strata), which makes use of these methods of calculating variance inappropriate. We suggest the use of a method called "delete-a-group" jackknife to estimate the variance of population attributable risk when a complex survey design has been implemented. We demonstrate the method using an example of Johne's disease. Advantages of the "delete-a-group" jackknife method include simplicity of implementation and flexibility to estimate variance for any point estimate of interest.     

Effects of anti-inflammatory drugs on lipopolysaccharide-challenged and -unchallenged equine synovial explants

OBJECTIVE: To evaluate the effects of anti-inflammatory drugs on lipopolysaccharide (LPS)-challenged and -unchallenged equine synovial membrane in terms of production of prostaglandin E2 (PGE2) and hyaluronan, viability, and histomorphologic characteristics. SAMPLE POPULATION: Synovial membranes were collected from the carpal, tarsocrural, and femoropatellar joints of 6 adult horses. PROCEDURE: Synovial membranes from each horse were minced and pooled and explants were treated with one of the following: no drug (control), drug, LPS alone, or LPS and drug. Treatment drugs were phenylbutazone (PBZ), flunixin meglumine (FNX), ketoprofen (KET), carprofen (CRP), meloxicam (MEL), low-concentration methylprednisolone (METH), high-concentration METH, dimethyl sulfoxide (DMSO), or an experimental COX-2 inhibitor (dissolved in DMSO). Following 48 hours of culture, medium was assayed for PGE2 and hyaluronan concentration. Synovial explants were assessed for viability and histomorphologic characteristics. RESULTS: For the LPS-challenged explants, PBZ, FNX, KTP CRF MEL, and low-concentration METH suppressed PGE2 production, compared with LPS challenge alone. Only MEL suppressed PGE2 production from LPS-challenged explants, compared with unchallenged explants. Synovial explants maintained > 90% viability and there was no significant difference in viability or hyaluronan production among explants. Histomorphologic scores were significantly decreased for explants treated with low-concentration METH or DMSO. CONCLUSIONS AND CLINICAL RELEVANCE: PBZ, FNX, KTP, CRFP MEL, and low-concentration METH suppressed PGE2 production in LPS-challenged explants. Meloxicam appeared to have more selective suppression of COX-2 activity. Histomorphologic scores suggest detrimental effects of METH, DMSO, and the experimental COX-2 inhibitor. Commonly used nonsteroidal anti-inflammatory drugs suppress induced synovial membrane PGE2 production without detrimental effects on synovial membrane viability and function.     

Performance of light vs heavy steers grazing Plains Old World bluestem at three stocking rates

Live weight gains of light and heavy calves grazing Plains Old World bluestem at three stocking rates were evaluated during the summers of 1997 and 1998. Initial weights of mixed-breed light-weight steers (LHT) were 141 SD = 17 kg (n = 214) in 1997 and 160 SD = 23 kg (n = 193) in 1998. Initial weights of mixed-breed heavy steers (HWT) were 265 SD = 17 kg (n = 115) in 1997 and 248 SD = 13 kg (n = 126) in 1998. Initial stocking rates for both sizes of steers were as follows: light, 392 kg of live weight/ha; moderate, 504 kg of live weight/ha (increased to 616 kg live weight/ha in 1998); and heavy, 840 kg of live weight/ ha. Averaged gain and gain/hectare are reported as stocking rate by steer type within year. Heavy steers had greater ADG than LHT steers during both years. Forage intake, expressed as a percentage of BW, was greater (P = 0.05) for LHT (3.1%) than for HWT (2.8%) calves. Grazing time (min/d; 1998 only) was greater (P = 0.05) for LHT (665) than for HWT (624) steers. Forage CP and in vivo digestible organic matter (DOM) were slightly greater (P < 0.05) in pastures grazed by HWT vs LHT cattle. Gain/hectare was greater (P < 0.05) for LHT than for HWT calves at all three stocking rates during both years. A linear decline in ADG was observed (P < 0.07) as stocking rates increased for HWT steers in 1997 and LHT steers in 1998. However, ADG did not decline with increasing stocking rate for LHT calves during 1997 or HWT calves during 1998. Forage intake was not different among stocking rates in either 1997 or 1998. Grazing time was greatest (P < 0.05) for steers in the moderate and heavy stocking rates. Forage in vivo DOM decreased (P < 0.05) as stocking rate increased. Both LHT and HWT steers had lower (P < 0.05) ADG at all three stocking rates during 1998 compared with 1997. Despite lower ADG, LHT steers had greater gain/hectare than HWT steers during both 1997 and 1998.     

Intraosseous approach to the nasolacrimal duct for removal of a foreign body in a dog

A Labrador retriever was evaluated because of chronic mucopurulent discharge from the left eye. A foreign body was identified in the nasolacrimal duct by use of dacryocystorhinography. Attempts to alleviate the inflammation by use of flushing and administration of antimicrobials were unsuccessful. At surgery, the infraorbital foramen was used as a landmark for a skin incision, because the nasolacrimal duct courses dorsal and parallel to the infraorbital canal. An air drill was used to remove the portion of the maxillary bone overlying the nasolacrimal duct, which exposed the intraosseous portion of the duct and allowed removal of a plant-material foreign body. The incision in the duct was allowed to heal by second intention, and the dog recovered without complications.     

Phosphorus bioavailability, growth performance, and nutrient balance in pigs fed high available phosphorus corn and phytase

Three experiments were conducted to evaluate P bioavailability, growth performance, and nutrient balance in pigs fed high available P (HAP) corn with or without phytase. The bioavailability of P in normal and HAP corn relative to monosodiumphosphate (MSP) for pigs was assessed in Exp. 1. In a randomized complete block design, 96 pigs (average initial BW 9.75 kg) were fed eight diets for 28 d. The reference and test diets were formulated by adding P as MSP, HAP, or normal corn at 0, 0.75, or 1.5 g/kg to a corn-starch-soybean meal basal diet (2.5 g/kg P) at the expense of cornstarch. Plasma inorganic P concentration responded linearly (P < 0.05) to supplemental P intake. Estimates of P bioavailability from HAP andnormal corn when plasma P was regressed on supplemental P intake were 46 and 33%, respectively. In Exp. 2 and 3, pigs were fed corn-soybean meal-based diets containing HAP corn or normal corn and 0 or 600 units of phytase per kilogram in a 2 x 2 factorial arrangement (two corn sources and two levels of phytase). In Exp. 2, 48 crossbred pigs (barrow:gilt, 1:1) averaging 9.25 kg were used to evaluate growth performance. There were no detectable interactions between corn source and phytase for any of the performance criteria measured. Pigs receiving normal corn had the lowest (P < 0.05) BW and rate of gain. Feed efficiency was lower (P < 0.05) in pigs fed normal compared with those fed the HAP corn phytase-supplemented diet. In Exp. 3, 24 crossbred barrows averaging 14.0 kg were used to evaluate nutrient digestibility. There were no detectable interactions between corn and phytase for any of the N and Ca balance criteria. Nitrogen and Ca retention were improved in pigs receiving HAP corn with phytase (P < 0.05). Retention and digestibility of P was lowest (P < 0.01) for pigs on normal corn diet without phytase. The percentage of P digested and retained was improved and fecal P excretion lowered (P < 0.05) by feeding HAP corn.The results of this study indicate that the bioavailability and balance of P in HAP corn is superior to that of normal corn. The addition of 600 phytase units (Natuphos 600, BASF) to HAP corn-based diets further improved P digestibility and reduced P excretion in pigs.     

Long‐Term Effect of Deslorelin Implant on Ovarian Pre‐Antral Follicles and Uterine Histology in Female Rats

The objective of the present study was to investigate the inhibitory effects of long‐term deslorelin implant administration on the ovarian and uterine structures of female rats. A total of 16 non‐pregnant female rats were randomly assigned to two groups, each consisting of eight animals. Animals in the implant group (DESL) received subcutaneously (s.c.) a single deslorelin implant (4.7 mg), an analogue of GnRH, while no treatment was applied to the control group (CON). A single adult male rat was introduced into the cages of both the DESL and CON females after 6 weeks of implant administration. After 1 year of implant administration, all animals were killed and follicular structures and volumes of ovaries and uterus were examined using stereological methods. Stereological observations showed that the mean ovarian total volume of the DESL group (0.28 ± 0.07 cm3) was lower than that of the CON group (1.55 ± 0.23 cm3) (p < 0.001). On the other hand, the total number of pre‐antral follicles in the ovaries of DESL (555.32 ± 151.47) females were significantly lower than the control group (1162.96 ± 189.19) (p < 0.001). In the DESL group, the mean volumes of epithelium, endometrium, myometrium and total volume of the uterus were significantly (p < 0.001) lower than in the control groups. In conclusion, these findings indicate that the long‐term deslorelin implant (i) interferes with the normal cyclicity of female rats and (ii) affects the pre‐antral follicle population. Further studies will be required to determine the effects of long‐term deslorelin treatment on the pre‐antral follicle numbers and future fertility in other species.