The effects of equine skin preparation on transdermal drug penetration in vitro

An increasing number of formulations are applied to equine skin, yet variable penetration can affect efficacy, or the incidence of adverse effects, or both. To investigate the effects of common methods of skin preparation on transdermal drug penetration in vitro, we clipped, harvested, and froze skin samples from 5 Thoroughbred geldings. Thawed samples were prepared as follows: control (no preparation); cleaned with aqueous chlorhexidine (Aq-C, 0.1% w/v); cleaned with alcoholic chlorhexidine (Al-C, 0.5% w/v); shaved (Sh); or tape-stripped (Ta) with the use of adhesive tape. The samples were then placed in diffusion cells, and 2 g of methylsalicylate (MeSa) gel (Dencorub) was applied to the stratum corneum side. The penetration of MeSa and its analyte, salicylate (Sa), through the skin samples was measured over 10 h. Compared with control skin, significantly more MeSa penetrated through skin prepared with Al-C or Sh (P < 0.01) or with Aq-C or Ta (P < 0.05), and significantly more Sa was recovered in the receptor phase from skin prepared with Aq-C, Al-C, or Sh (P < 0.05) or with Ta (P < 0.01). A significantly higher rate of penetration and shorter lag time were also noted for MeSa with all the prepared skin samples, compared with the control samples. The results show that clinical techniques routinely used to clean or prepare skin can significantly affect the rate and extent of penetration of a topically applied drug. This may result in greater systemic availability of active drug, which could lead to enhanced efficacy and, possibly, a higher incidence of adverse effects.     

Regional differences in the in vitro penetration of hydrocortisone through equine skin

Little is known about the transdermal penetration of hydrocortisone in the horse and, although commercial formulations containing hydrocortisone are registered for topical use in the horse, there have been no studies investigating the movement of this glucocorticoid through different regions of equine skin. Skin was harvested from the thorax, groin and leg (dorsal metacarpal) regions of five Thoroughbred geldings and frozen (-20 degrees C) until required. Defrosted skin was placed in Franz-type diffusion cells and the amount of radiolabelled ((3)H) hydrocortisone, in a saturated solution of unlabelled hydrocortisone in 50% ethanol (w/w), which penetrated through and remained within skin samples was measured over 24 h. Significantly higher (P < 0.001) maximum flux (J(max); mol/cm(2)/h) was measured when hydrocortisone was applied to skin from the leg, compared to thorax and groin, although significantly less hydrocortisone (P < 0.001) was retained within skin from the leg at 24 h. Topical application of hydrocortisone in a vehicle containing ethanol would penetrate faster through leg skin from the lower leg when compared with the thorax or groin, which depending on cutaneous blood flow, may result in higher systemic drug concentrations or greater efficiency in treating local inflamed tissue.     

Regional differences in transdermal penetration of fentanyl through equine skin

The rate and regional differences for the penetration of fentanyl through equine skin was investigated in vitro using a commercial transdermal therapeutic system (TTS) or ‘patch’. Skin collected from the thorax, groin and leg (dorsal metacarpal) regions of five horses was placed in diffusion cells and a fentanyl TTS applied to each skin sample. Drug penetration through each skin sample over 48 h measured using high performance liquid chromatography (HPLC). Cumulative penetration (μg/cm²) was plotted against time (h) and used to regress the steady state flux (μg/cm²/h) of fentanyl through each skin site. Results showed similar fluxes for both the thorax (2.32 ± 0.17 μg/cm²/h and groin (2.21 ± 0.11 (μg/cm²/h) regions, but significantly lower flux (P = < 0.05) for the leg region (1.56 ± 0.120 μg/cm²/h. Interestingly, there was a significantly longer lag time for the penetration of fentanyl through the groin region (7.87 ± 0.51 h) compared to the other two sites (5.66 ± 0.97 h and 5.75 ± 0.43 h for the thorax and leg regions respectively). The results suggest that a fentanyl TTS applied to the leg region may have a small but significantly lower amount of fentanyl available systemically, compared to patches applied to the thorax or groin regions, which may affect the level of analgesia subsequently achieved in the horse.     

The effect of region of application on absorption of ethanol and hexanol through canine skin

The effect of region of application on the percutaneous penetration of solutes with differing lipophilicity was investigated in canine skin. Skin from the thorax, neck, back, groin, and axilla regions was harvested from Greyhound dogs and placed in Franz-type diffusion cells. Radiolabelled (14C) ethanol (Log P 0.19) or hexanol (Log P 1.94) was applied to each skin section for a total of 5h. The permeability coefficient (kP, cm h(-1)) and residue of alcohol remaining in the skin were significantly (P=0.001) higher for hexanol compared to ethanol. In contrast, ethanol had a far greater maximum flux (Jmax, mol (cm2)(-1) h(-1)) than hexanol (P=0.001). A comparison of regional differences shows the kP and Jmax for ethanol in the groin was significantly lower (P=0.035) than the back. The kP and Jmax for hexanol were significantly higher (P=0.001) in the axilla than the other four skin sites. An understanding of factors influencing percutaneous drug movement is important when formulating topical preparations for the dog.     

Effects of vehicle and region of application on absorption of hydrocortisone through canine skin

OBJECTIVE: To determine the effects of various vehicles on the penetration and retention of hydrocortisone applied to canine skin. SAMPLE POPULATION: 20 canine skin samples obtained from the thorax, neck, and groin regions of 5 Greyhounds. PROCEDURE: Skin was harvested from dogs after euthanasia and stored at -20 degrees C until required.The skin was then defrosted and placed into diffusion cells, which were maintained at approximately 32 degrees C by a water bath. Saturated solutions of hydrocortisone that contained trace amounts of radiolabelled [14C]-hydrocortisone in each vehicle (ie, PBS solution [PBSS] alone, 50% ethanol [EtOH] in PBSS [wt/wt], and 50% propylene glycol in PBSS [wt/wt]) were applied to the outer (stratum corneum) surface of each skin sample, and aliquots of receptor fluid were collected for 24 hours and analyzed for hydrocortisone. RESULTS: The maximum flux of hydrocortisone was significantly higher for all sites when dissolved in a vehicle containing 50% EtOH, compared with PBSS alone or 50% propylene glycol, with differences more prominent in skin from the neck region. In contrast, higher residues of hydrocortisone were found remaining within the skin when PBSS alone was used as a vehicle, particularly in skin from the thorax and neck. CONCLUSIONS AND CLINICAL RELEVANCE: Penetration of topically applied hydrocortisone is enhanced when EtOH is used in vehicle formulation. Significant regional differences (ie, among the thorax, neck, and groin areas) are also found in the transdermal penetration and skin retention of hydrocortisone. Variability in clinical response to hydrocortisone can be expected in relation to formulation design and site of application.     

Regional variations in percutaneous absorption of methimazole: an in vitro study on cat skin

The use of transdermal gel medications in cats has become popular in veterinary medicine due to the ease of administration compared to oral medication. The research to support systemic absorption of drugs after transdermal gel administration and the preferred skin region to apply these drugs in cats is limited. The aim of this study was to characterize the effect of different skin regions on the percutaneous absorption pharmacokinetics of a commercially available transdermal methimazole after a finite dose was applied to feline skin in vitro. A commercial formulation of methimazole (10 mg) was applied to four skin regions (the inner stratum corneum of the ear, groin, neck, and thorax regions) from six cats. The receptor medium was sampled up to 36 h postapplication, and methimazole concentrations were measured using high‐performance liquid chromatography. Methimazole was absorbed more completely across the pinnal skin, compared to the groin, neck, and thorax (P < 0.001), which justifies application to the pinna to maximize efficacy and also to minimize the effects of grooming.     

The effects of vehicle and region of application on in vitro penetration of testosterone through canine skin

The effects of the vehicles phosphate-buffered saline (PBS), ethanol (EtOH; 50% in PBS w/w) and propylene glycol (PG; 50% in PBS w/w) and the region of administration on in vitro transdermal penetration of testosterone was investigated in the dog. Skin was harvested from the thorax, neck (dorsal part) and groin regions of greyhounds after euthanasia and stored at -20 degrees C until required. The skin was then de-frosted and placed into Franz-type diffusion cells which were maintained at approximately 32 degrees C by a water-bath. Saturated solutions of testosterone, containing trace amounts of radiolabelled (14C) testosterone, in each vehicle were applied to the outer (stratum corneum) surface of each skin sample and aliquots of receptor fluid were collected at 0, 2, 4, 8, 16, 20, 22 and 24h and analysed for testosterone by scintillation counting. The maximum flux (J(max)) of testosterone was significantly higher for all sites when dissolved in a vehicle containing 50% EtOH or 50% PG, compared to PBS. In contrast, higher residues of testosterone were found remaining within the skin when PBS was used as a vehicle. This study shows that variability in percutaneous penetration of testosterone could be expected with formulation design and site of application.     

Investigation of in vitro transdermal absorption of fentanyl from patches placed on skin samples obtained from various anatomic regions of dogs

OBJECTIVE: To investigate in vitro transdermal absorption of fentanyl from patches through skin samples obtained from various anatomic regions of dogs. SAMPLE POPULATION: Skin samples from 5 Greyhounds. PROCEDURE: Skin samples from the dogs' thoracic, neck, and groin regions were collected postmortem and frozen. After samples were thawed, circular sections were cut and placed in Franz-type diffusion cells in a water bath (32 degrees C). A commercial fentanyl patch, attached to an acetate strip with a circular hole, was applied to each skin sample. Cellulose strips were used as control membranes. Samples of receptor fluid in the diffusion cells were collected at intervals for 48 hours, and fentanyl concentrations were analyzed by use of high-performance liquid chromatography. RESULTS: Mean+/-SD release rate of fentanyl from the patch, defined by its absorption rate through the non-rate-limiting cellulose membrane, was linear during the first 8 hours (2.01+/-0.05 microg/cm2 of cellulose membrane/h) and then decreased. Fentanyl passed through skin from the groin region at a faster rate and with a significantly shorter lag time, compared with findings in neck or thoracic skin samples. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro, fentanyl from a patch was absorbed more quickly and to a greater extent through skin collected from the groin region of dogs, compared with skin samples from the thoracic and neck regions. Placement of fentanyl patches in the groin region of dogs may decrease the lag time to achieve analgesia perioperatively; however, in vivo studies are necessary to confirm these findings.     

薄荷醇和氮酮对甲硝唑在犬中体外透皮吸收的影响

研究不同的溶液载体（PBS,5％薄荷醇和5％氮酮）和不同部位的皮肤对甲硝唑在犬中体外透皮吸收和皮内摄取的影响。取下北京犬颈部、胸部以及腹部皮肤,-20℃保存。使用时,皮肤解冻固定在改良Franz透皮扩散仪上,保持恒速（200±1）r／min,恒温（35±0．5）℃。在扩散池中的皮肤角质层上加入2mL溶液载体（含甲硝唑58．4μmol）,以20％乙醇为溶剂溶解薄荷醇和氮酮,在预定时间点取样1mL,采用HPLC方法测定各接受液中的药物量和皮肤中摄取的药物量。结果显示,与PBS相比,薄荷醇和氮酮能增加所有部位甲硝唑的透皮吸收量和皮内摄取量（P〈0．05）。同一溶液载体在不同部位的渗透性存在差异,腹部〉颈部〉胸部,不同部位的皮内摄取量也存在差异,颈部〉胸部〉腹部。说明甲硝唑在不同溶液载体和不同部位皮肤的渗透性存在差异。     

Assessment of a correlation between Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) and selected biophysical skin measures (skin hydration,pH, and erythema intensity) in dogs with naturally occurring atopic dermatitis

Atopic dermatitis is a common allergic skin disease in dogs. The aim of this study was to examine the possibility of a correlation between biophysical skin variables: skin hydration (SH), skin pH, and erythema intensity measured in 10 different body regions and both total Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) and CADESI measured in a given region (CADESI L). The study was conducted using 33 dogs with atopic dermatitis. The assessment of the biophysical variables was done in 10 body regions: the lumbar region, right axillary fossa, right inguinal region, ventral abdominal region, right lateral thorax region, internal surface of the auricle, interdigital region of right forelimb, cheek, bridge of nose, and lateral site of antebrachum. Positive correlations were found between SH and CADESI L for the following regions: the inguinal region (r = 0.73) and the interdigital region (r = 0.82), as well as between total CADESI and SH on digital region (r = 0.52). Also, positive correlations were reported for skin pH and CADESI L in the lumbar region (r = 0.57), the right lateral thorax region (r = 0.40), and the lateral antebrachum (r = 0.35). Positive correlations were found in the interdigital region between erythema intensity and the total CADESI-03 (r = 0.60) as well as the CADESI L (r = 0.7). The results obtained suggest that it may be possible to use skin hydration, pH, and erythema intensity to assess the severity of skin lesion but positive correlation was only found in < 13.3% of possible correlations and usage of these measures in dogs is limited.     

Effect of solute lipophilicity on penetration through canine skin

OBJECTIVE: To investigate the effect of lipophilicity on the percutaneous penetration of a homologous series of alcohols through canine skin. DESIGN: Skin harvested from Greyhound thorax was placed in Franz-type diffusion cells and the in vitro passage of radiolabelled (14C) alcohols (ethanol, butanol, hexanol and octanol (Log P 0.19-3.0)) through separate skin sections was measured in replicates of five. Permeability coefficient (kP, cm/h), maximum flux (Jmax, mol/cm2/h) and residue remaining within the skin were determined. RESULTS: The kP increased with increasing lipophilicity (6.2 x 10(-4) +/- 1.6 x 10(-4) cm/h for ethanol to 1.8 x 10(-2) +/- 3.6 x 10(-3) cm/h for octanol). Alcohol residues remaining within each skin sample followed a similar pattern. An exponential decrease in Jmax with increasing lipophilicity was observed. CONCLUSION: Changes in canine skin permeability occur with increasing alcohol lipophilicity. This finding has practical consequences for the design of topical formulations and optimisation of drug delivery through animal skin.     

The examination of biophysical parameters of skin (transepidermal water loss, skin hydration and pH value) in different body regions of normal cats of both sexes

The purpose of this study was to evaluate transepidermal water loss (TEWL), skin hydration and skin pH in normal cats. Twenty shorthaired European cats of both sexes were examined in the study. Measurements were taken from five different sites: the lumbar region, the axillary fossa, the inguinal region, the ventral abdominal region and the left thoracic region. In each of the regions, TEWL, skin hydration and skin pH were measured. The highest TEWL value was observed in the axillary fossa (18.22g/h/m(2)) and the lowest in the lumbar region (10.53g/h/m(2)). The highest skin hydration was found in the inguinal region (18.29CU) and the lowest in the lumbar region (4.62CU). The highest skin pH was observed in the inguinal region (6.64) and the lowest in the lumbar region (6.39). Statistically significant differences in TEWL were observed between the lumbar region and the left side of the thorax region (P=0.016), the axillary fossa (P=0.0004), the ventral region (P=0.005), and the inguinal region (P=0.009). There were significant differences in skin hydration between the lumbar region and the left thorax (P=0.000003), the axillary fossa (P=0.002), the ventral abdomen (P=0.03), and the inguinal region (P=0.0003) as well as between the thorax and the ventral abdomen (P=0.005). TEWL was higher in females (15g/h/m(2)) than in males (4.57g/h/m(2)). Skin hydration was higher in females (13.89CU) than in males (12.28CU). Significant differences were not found between males and females for TEWL and skin hydration. Skin pH was higher in males (6.94) than in females (6.54), which was significant (P=0.004).     

Use of chromametry and digital photography for objective measurement of skin color in clinically normal dogs

OBJECTIVE: To evaluate whether skin erythema in clinically normal dogs can be quantified by use of chromametry and image analysis of digital photographs. ANIMALS: 9 German Shepherd Dogs and 10 mixed-breed dogs. PROCEDURE: Hair was clipped at 7 sites on the body. Skin erythema was evaluated at the axillary region, right and left lateral aspect of thorax, right and left loin area (ie, part of the back between the thorax and pelvis), right and left groin area (ie, the junctional region between the abdomen and thigh), metatarsal digital pad, and on the nose. Replicate measurements were done by use of chromametry and image analysis of digital photographs, using erythema values in accordance with the Committee International d'Eclairage (CIE)-Lab color system. RESULTS: Repeatability was high for both techniques. Within-dog variation was lower than between-dog variation. Between-dog variation was high for both groups of dogs. Interregional variation was significant in German Shepherd Dogs and mixed-breed dogs. Erythema values revealed symmetry between the right and left lateral aspects of the thorax and loin and groin areas. CONCLUSIONS AND CLINICAL RELEVANCE: Precise objective methods are available for skin erythema quantification. Chromametric and photographic erythema values had a high within-dog reproducibility. Between-dog variability was high for German Shepherd Dogs and mixed-breed dogs as was regional variation, indicating differences in color among dogs.     

Plasma salicylate concentrations in immature dogs following aspirin administration: comparison with adult dogs

Aspirin disposition in immature and adult dogs, assessed by plasma salicylate concentrations following single doses of aspirin given orally (p.o.) and intravenously (i.v.), was compared. Using a cross-over design, four immature (12–16-weeks-old) and eight adult (1– 2-years-old) dogs were given a single dose of aspirin at 17.5 mg/kg body weight i.v. and a single dose of buffered aspirin at 35 mg/kg body weight p.o. Blood was collected from the jugular vein for 24 h following each dose. A fluorescence polarization immunoassay was used for determination of salicylate in plasma. Significant differences in aspirin disposition were identified between the two groups. Immature dogs had significantly shorter salicylate half-life, lower mean residence time, and more rapid salicylate clearance than adult dogs. The difference in volume of distribution between the two groups was not significantly different. Immature dogs had lower mean (± SD) peak plasma salicylate concentrations (64.5 ± 2.38 mg/L) than adult dogs (95.9 ± 12.2 mg/L) following a single oral dose of buffered aspirin at 35 mg/kg body weight. Predicted plasma salicylate concentration-time curves were constructed for various aspirin dosage regimens. This analysis showed that the previously recommended buffered aspirin dose for adult dogs of 25 mg/kg body weight p.o. every 8 h would be ineffective in maintaining plasma salicylate concentrations > 50 mg/L in immature dogs.     

Disposition of sodium salicylate,flunixin and meloxicam after intravenous administration in broiler chickens

Three nonsteroidal anti-inflammatory drugs (NSAIDs) [sodium salicylate, flunixin (FLU) and meloxicam (MEL)] were administered intravenously to broiler chickens. Plasma concentrations were determined by high-performance liquid chromatography methods and pharmacokinetic parameters were calculated. After intravenous administration of sodium salicylate (50 mg/kg), FLU (1.1 mg/kg) and MEL (0.5 mg/kg), these drugs were eliminated from plasma with a mean half-life of 04.04, 05.45 and 03.20 h, respectively. Apparent volumes of distribution (0.39, 0.08 and 0.12 L/kg, respectively) indicated that tissue distribution was limited for the three drugs. Total body clearance was 70 mL/h.kg for sodium salicylate and 10 and 25 mL/kg.h for FLU and MEL, respectively. Based on the pharmacokinetic parameters these NSAIDs may offer possibilities for treatment of various conditions in chickens.     

Pharmacokinetics of marbofloxacin in dogs after oral and parenteral administration

Six dogs were treated with a single intravenous (i.v.) dose (2 mg/kg) of marbofloxacin, followed by single oral (p.o.) doses of marbofloxacin at 1, 2 and 4 mg/kg, according to a three-way crossover design. The same experimental design was used for the subcutaneous (s.c.) route. In addition, a long-term trial involving eight dogs given oral doses of marbofloxacin at 2, 4 and 6 mg/kg/day for thirteen weeks was carried out. Plasma and urine samples were collected during the first two trials, plasma and skin samples were collected after the second of these trials. Plasma, urine and skin concentrations of marbofloxacin were determined by a reverse phase liquid chromatographic method. Mean pharmacokinetic parameters after i.v. administration were the following: t1/2β=12.4h; Cl _B= 0.10 L/h.kg; V _area= 1.9 L/kg. The oral bioavailability of marbofloxacin was close to 100% for the three doses. At 2 mg/kg, C _max of 1.4 μg/mL was reached at t _max of 2.5 h. Mean AUC and C _max values had a statistically significant linear relationship with the doses administered. About 40% of the administered dose was excreted in urine as unchanged parent drug. After s.c. administration, the calculated parameters were close to those obtained after oral administration, except t _max (about 1 h) which was shorter. The mean skin to plasma concentration ratio after the long-term trial was 1.6, suggesting good tissue penetration of marbofloxacin.     

The pharmacokinetics of salicylate in dairy cattle are not altered by simultaneous intravenous ceftiofur sodium and DL-lysine-acetyl salicylate (Aspirin)

This study evaluated potential alterations to the pharmacokinetics of salicylate by concurrently administered ceftiofur sodium. The trial design was a crossover using 10 non-lactating, non-pregnant dairy cows. In the first period each cow received intravenously (IV) 26 mg/kg of DL-lysine acetyl salicylate (aspirin) followed immediately by 2 mg/kg ceftiofur sodium. In the second period each cow received 26 mg/kg of aspirin IV. Plasma samples were harvested for determination of salicylate concentration by HPLC. The data best fitted a single compartment open model, using weighted non-linear regression. No alterations to the pharmacokinetic parameters of salicylate in cattle by concurrently administered ceftiofur sodium were detected ( P <0.05). Using 90% confidence intervals, and testing for changes of > 20%. control values, elimination half-life ( t ₁/₂), apparent volume of distribution ( V _d), area under the plasma concentration versus time curve ( AUC ) and mean residence time ( MRT ) were not altered. For control animals the elimination rate constant ( k _el) and total body clearance ( Cl ) were 1.35/pm0.43 h⁻¹ and 20.2/pm6.1 ml/h.kg respectively (mean/pmSD). Since ceftiofur sodium did not affect the pharmacokinetics of salicylate, dose regimens for aspirin in cattle need not be altered when ceftiofur sodium is administered concurrently.     

Pharmacokinetics and dosage regimen of cefotaxime in cross-bred calves following single intramuscular administration

The pharmacokinetics, penetration into erythrocytes and plasma protein binding of cefotaxime were investigated in cross-bred calves. Following a single intramuscular dose of cefotaxime (10 mg/kg), the absorption half-life and elimination half-life were 0.13±0.03 h and 2.97±0.72 h, respectively. The apparent volume of distribution and total body clearance were 3.28±0.72 L/kg and 0.78±0.08 L/kg per h, respectively. The extent of penetration into erythrocytes was 24–40% of the total blood concentration. Cefotaxime was bound to plasma proteins of calves to the extent of 25.5–33.6%. A satisfactory intramuscular dosage regimen for cefotaxime in calves would be 11 mg/kg followed by 10 mg/kg at 7 h intervals.Abbreviations ATCC American type cell culture - MIC minimum inhibitory concentration - PCV packed cell volume     

Cutaneous innervation of the thorax and abdomen of the dog

The anatomy of the cutaneous nerves innervating the canine thorax and abdomen was investigated by gross dissection of 38 dogs. Additionally, the cutaneous areas innervated by the thoracic and abdominal cutaneous nerves were mapped in a 2nd group of 33 barbiturate-anesthetized male dogs, using electrophysiologic techniques. The skin of the thorax was innervated by dorsal cutaneous branches, lateral cutaneous branches, and ventral cutaneous branches of the spinal nerves. The dorsal cutaneous branches were branches of the dorsal primary branches of spinal nerves C6 and T2 through T11. The lateral cutaneous branches were branches of the ventral primary branches of spinal nerves T2 through T12. The ventral cutaneous branches were branches of the ventral primary branches of spinal nerves T2 through T10. The skin of the abdomen was innervated by dorsal and lateral cutaneous branches of spinal nerves T12 through L3 (and occasionally L4). The cutaneous areas of the dorsal cutaneous branches occupied the dorsal half of the scapular and thoracic regions and the dorsal 2/5 of the abdominal region. The cutaneous areas of the lateral cutaneous branches covered the major portion of the ventral half of the thorax and the ventral 3/5 of the abdomen. The cutaneous areas of the ventral cutaneous branches occupied the axilla and the ventral part of the thoracic wall.     

Attenuation of acute plasma cortisol response in calves following intravenous sodium salicylate administration prior to castration

Pain associated with castration in cattle is an animal welfare concern in beef production. This study examined the effect of oral aspirin and intravenous (i.v.) sodium salicylate on acute plasma cortisol response following surgical castration. Twenty bulls, randomly assigned to the following groups, (i) uncastrated, untreated controls, (ii) castrated, untreated controls, (iii) 50 mg/kg sodium salicylate i.v. precastration and (iv) 50 mg/kg aspirin (acetylsalicylic acid) per os precastration, were blood sampled at 3, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 4, 6, 8, 10 and 12 h postcastration. Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. Data were analyzed using noncompartmental analysis, a simple cosine model, anova and t -tests. Intravenous salicylate V _d(ss) was 0.18 L/kg, Cl _B was 3.36 mL/min/kg and t _{1/2 λ} was 0.63 h. Plasma salicylate concentrations above 25  μ g/mL coincided with significant attenuation in peak cortisol concentrations ( P  = 0.029). Peak salicylate concentrations following oral aspirin administration was <10  μ g/mL and failed to attenuate cortisol response. Once salicylate concentrations decreased below 5  μ g/mL, cortisol response in the castrated groups was significantly higher than uncastrated controls ( P  = 0.018). These findings have implications for designing drug regimens to provide analgesia during routine animal husbandry procedures.