Pharmacokinetics of antipyrine and sulphadimidine (sulfamethazine) in camels, sheep and goats

The pharmacokinetics of antipyrine and sulphadimidine were studied in male camels, sheep and goats. The two drugs were administered concomitantly. Following intravenous injection of antipyrine (25 mg/kg) and sulphadimidine (sulfamethazine) (100 mg/kg), the pharmacokinetics of the two drugs were adequately described by a one-compartment model. Antipyrine half-life in goats (2.58 h) was shorter than that in sheep (4.04 h) and camels (18.78 h). The plasma clearance was greatest in goats then sheep and then camels. For sulphadimidine, a significantly greater volume of distribution was observed in camels and the greatest plasma clearance and shortest half-life were reported in goats. Sulphadimidine half-life was 2.77 h in goats, 4.72 h in sheep and 7.36 h in camels. The present results suggest that goats have the fastest elimination of these drugs from the circulation, followed by sheep and then camels.     

Pharmacokinetics of enrofloxacin after intravenous and intramuscular administration in Angora goats.

Pharmacokinetics and bioavailability of enrofloxacin were determined after single intravenous (IV) and intramuscular (IM) administrations of 5 mg/kg body weight (BW) to 5 healthy adult Angora goats. Plasma enrofloxacin concentrations were measured by high performance liquid chromatography. Pharmacokinetics were best described by a 2-compartment open model. The elimination half-life and volume of distribution after IV and IM administrations were similar (t1/2beta, 4.0 to 4.7 h and Vd(ss),1.2 to 1.5 L/kg, respectively). Enrofloxacin was rapidly (t1/2a, 0.25 h) and almost completely absorbed (F, 90%) after IM administration. Mean plasma concentrations of enrofloxacin at 24 h after IV and IM administration (0.07 and 0.09 microg/mL, respectively) were higher than the minimal inhibitory concentration (MIC) values for most pathogens. In conclusion, once-daily IV and IM administration of enrofloxacin (5 mg/kg BW) in Angora goats may be useful in treatment of infectious diseases caused by sensitive pathogens.     

Pharmacokinetics and bioavailability of nimesulide in goats

The pharmacokinetic properties and bioavailability of cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drug nimesulide were investigated in female goats following intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 4 mg/kg BW. Blood samples were collected by jugular venipuncture at predetermined times after drug administration. Plasma concentrations of nimesulide were determined by a validated high-performance liquid chromatography method. Plasma concentration-time data were subjected to compartmental analysis and pharmacokinetic parameters for nimesulide after i.v. and i.m. administration were calculated according to two- and one-compartment open models respectively. Following i.v. administration, a rapid distribution phase was followed by the slower elimination phase. The half-lives during the distribution phase (t1/2alpha) and terminal elimination phase (t1/2beta) were 0.11+/-0.10 and 7.99+/-2.23 h respectively. The steady-state volume of distribution (Vd(ss)), total body clearance (ClB) and mean residence time (MRT) of nimesulide were 0.64+/-0.13 L/kg, 0.06+/-0.02 L/h/kg and 11.72+/-3.42 h respectively. After i.m. administration, maximum plasma concentration (Cmax) of nimesulide was 2.83+/-1.11 microg/mL attained at 3.6+/-0.89 h (tmax). Plasma drug levels were detectable up to 72 h. Following i.m. injection, the t1/2beta and MRT of nimesulide were 1.63 and 1.73 times longer, respectively, than the i.v. administration. The bioavailability of nimesulide was 68.25% after i.m. administration at 4 mg/kg BW. These pharmacokinetic data suggest that nimesulide given intramuscularly may be useful in the treatment of inflammatory disease conditions in goats.     

Sulphadoxine and trimethoprim in goats and cows: absorption fraction, half-lives and the degrading effect of the ruminal flora

Oral administration of sulphadoxine to adult goats (100 mg/kg body weight) resulted in absorption of about two thirds from the gastrointestinal tract. The absorption rate was lowest in newborn kids and increased with increasing age. Following administration of sulphadoxine (40 mg/kg body weight) through a rumen fistula about 80% was absorbed in cows. Also the elimination rate for sulphadoxine was lower in newborn kids than in adult goats and increased with the age. Oral administration of the trimethorpim (TMP) to kids, goats (20 mg/kg body weight) and cows (8 mg/kg body weight) resulted in higher plasma concentrations in newborn kids than in the older age groups and the maximal concentration of TMP in the blood of adult goats and cows was lower than 0.2 μg/ml. In vitro experiments showed that trimethoprim may be degraded by ruminal microorganisms, but from experiments with oral administration of trimethoprim to cows it is concluded that metabolism in the cow's liver is at least as important as ruminal degradation.     

Effects of triiodothyronine treatment on pharmacokinetic properties and metabolite formation of antipyrine in dwarf goats.

The influence of triiodothyronine (5 micrograms/kg of body weight, sc, q 12 h for 7 days) on antipyrine (AP, 25 mg/kg, IV) plasma elimination and urinary metabolite excretion was studied in castrated male dwarf goats. After triiodothyronine treatment, a significant increase in AP elimination was found. However, the observed changes in clearances for production of AP metabolites (nor-AP, 3-hydroxymethyl-AP; 4-hydroxy-AP, and 4,4'-dihydroxy-AP) do not suggest a clear selectivity of triiodothyronine toward any of the metabolic pathways of AP.     

Comparative pharmacokinetics of diminazene in lactating goats and sheep

The pharmacokinetic aspects of diminazene aceturate were studied in lactating goats and sheep after single intravenous and intramuscular administrations of 3.5 mg/kg b.wt. Plasma and milk concentrations were determined by use of reversed phase high-performance liquid chromatography (HPLC) after ion-pair extraction. Following intravenous injection, the disposition of diminazene in goats and sheep conformed to a two-compartment model with rapid distribution and slower elimination phases. Values of (t1/2 beta) were obtained indicating a slower final disappearance of the drug from plasma of sheep (21.17 h) than in goats (16.39 h). Diminazene concentrations were maintained for more than 4 days in the plasma of goats and sheep. In both species of animals, diminazene was rapidly absorbed following intramuscular administration of 3.5 mg/kg b.wt. The peak plasma concentrations (Cmax) were 7.00 and 8.11 micrograms/ml and were attained at (Tmax) 0.92 and 1.12 hours in goats and sheep, respectively. The elimination half-life (t1/2el) of diminazene after intramuscular administration was shorter in goats (16.54 h) than in sheep (18.80 h). Systemic bioavailabilities (F%) of diminazene after intramuscular administration were 94.94% and 82.64% in goats and sheep, respectively. Diminazene could be detected in milk of goats and sheep within 10 min post-injection. Milk concentrations of the drug were lower in goats than in sheep and were detected for 5 and 6 days following both routes of administration, respectively.     

Effect of gonadal hormones on the plasma clearance and metabolite formation of antipyrine in the dwarf goat

The effect of gonadal hormones on the plasma elimination and urinary metabolite profile of antipyrine was studied in dwarf goats. Female goats were treated with testosterone and male goats were treated with 17β-oestradiol. Castrated males were treated with either testosterone or 17β-oestradiol. Antipyrine (25 mg/kg, i.v.) was given both before and after the hormonal treatments. The effects of the hormonal status on the plasma elimination of the parent compound were not consistent. This was possibly due to the fact that formation of the main metabolite of antipyrine in the goat, 4-hydroxy antipyrine (OHA), was not affected by sex or hormonal treatment. On the other hand, there were clear effects of hormonal status on urinary excretion of the three other metabolites. In females and castrated males testosterone suppressed the formation of norantipyrine (NORA), 3-hydroxymethylantipyrine (HMA) and 4,4'-dihydroxyantipyrine (DOHA). Intact males produced smaller amounts of these metabolites than females. It is concluded that distinct xenobiotic metabolizing pathways exist in the dwarf goat, which are influenced in their activity by gonadal hormones. This confirms previous findings in rats and mice. The possibility that sex hormones influence drug metabolism in food-producing animals could have consequences for veterinary therapeutics and public health. This study also demonstrates that, when using the antipyrine test for the assessment of hepatic drug metabolism, it is very important to include the determination of metabolites.     

Comparative aspects and sex differentiation of plasma sulfamethazine elimination and metabolite formation in rats, rabbits, dwarf goats, and cattle.

Plasma disposition and urinary recovery of sulfamethazine (SMZ), its N4-acetylated metabolite (N4AcSMZ), and 2 of its hydroxylated metabolites--5-hydroxysulfamethazine (5OHSMZ) and 6-hydroxymethylsulfamethazine (6CH2OHSMZ)--were determined in either sex of 4 animal species: rats, dwarf goats, rabbits, and cattle. Rats, rabbits, and dwarf goats had significant (P < 0.01) sex difference in SMZ plasma clearance. Male rats had higher plasma clearance than did female rats, and excreted higher amounts of the hydroxy metabolites and lower amounts of N4AcSMZ. The N4AcSMZ metabolite was predominant in plasma and urine of rabbits. Male rabbits had higher plasma clearance than did female rabbits, but differences in metabolite profile were not apparent. With regard to plasma SMZ elimination, the situation in goats was opposite to that in rats. Male goats had considerably lower clearance than did female goats. This was associated with a lower hydroxylation rat in males. Plasma half-life of SMZ in cows was lower than that in bulls, probably because of a smaller distribution volume in cows. Compared with elimination via urine, elimination via milk was negligible in cows. Significant differences in metabolite profiles were not found between bulls and cows. Similar to those in rats and mice, hormone-dependent xenobiotic metabolic pathways may exist in other species. Depending on species and xenobiotic compound residue concentrations of xenobiotics, their metabolites, or both may differ with sex of the animal, or may be altered after treatment with anabolic hormones.     

Effects of Ehrlichia phagocytophila infection on serum thyroid hormone concentrations and on antipyrine clearance and metabolite formation in dwarf goats.

The influence of infection with Ehrlichia phagocytophila (EP) on serum thyroid hormone concentrations and on antipyrine (25 mg/kg of body weight, IV) plasma elimination and urinary metabolite excretion was studied in castrated male dwarf goats. Mean thyroid hormone concentrations moderately decreased in EP-infected goats, with maximal decrease in total and free triiodothyronine and thyroxine serum concentrations of 56, 64, 23, and 19%, respectively. The estimated pharmacokinetic values of antipyrine (AP) in EP-infected goats were similar to those in the goats when healthy. However, glucuronidation of the AP-metabolites 3-hydroxymethyl-AP, 4,4'-dihydroxy-AP, and 4-hydroxy-AP was reduced during the febrile episode of the acute-phase response to EP infection.     

Blood and tissue concentrations of trimethoprim following its administration alone and in combination with josamycin.

Following a single oral dose of trimethoprim (10 mg/kg b. wt.) in normal fowls, the highest serum concentration achieved 4 hours post-administration with value of 0.64 microgram/ml. The absorption half-life time was 0.64 hours. The elimination half life was 4.73 hours. During repeated oral administration of 10 mg/kg b. wt., once daily for five consecutive days, trimethoprim peaked in serum, 4 h after each dose. Trimethoprim persisted in all fowl's tissues for 96 hours after stopping of drug administration. After oral administration of josamycin (18 mg/kg b. wt.) and trimethoprim (10 mg/kg b. wt.) in normal fowls, a maximum serum concentration of trimethoprim was recorded at 2 hours with half-life of absorption (t0.5(ab)) valued 0.74 hour. The elimination half-life (t0.5 beta) was 4.37 hours. During repeated oral administration of josamycin (18 mg/kg b. wt.) and trimethoprim (10 mg/kg b. wt.) once daily for five consecutive days in normal fowls, the highest plasma concentrations of trimethoprim occurred 2 hours post each dose. The daily maximum plasma concentrations during the repeated oral administration of both tested drugs were nearly constant.     

Effect of chronic lead intoxication on the distribution and elimination of amoxicillin in goats

A study of amoxicillin pharmacokinetics was conducted in healthy goats and goats with chronic lead intoxication. The intoxicated goats had increased serum concentrations of liver enzymes (alanine aminotransferase and γ-glutamyl transferase), blood urea nitrogen, and reactivated δ-aminolevulinic acid dehydratase compared to the controls. Following intravenous amoxicillin (10 mg/kg bw) in control and lead-intoxicated goats, elimination half-lives were 4.14 and 1.26 h, respectively. The volumes of distribution based on the terminal phase were 1.19 and 0.38 L/kg, respectively, and those at steady-state were 0.54 and 0.18 L/kg, respectively. After intramuscular (IM) amoxicillin (10 mg/kg bw) in lead-intoxicated goats and control animals, the absorption, distribution, and elimination of the drug were more rapid in lead-intoxicated goats than the controls. Peak serum concentrations of 21.89 and 12.19 µg/mL were achieved at 1 h and 2 h, respectively, in lead-intoxicated and control goats. Amoxicillin bioavailability in the lead-intoxicated goats decreased 20% compared to the controls. After amoxicillin, more of the drug was excreted in the urine from lead-intoxicated goats than the controls. Our results suggested that lead intoxication in goats increases the rate of amoxicillin absorption after IM administration and distribution and elimination. Thus, lead intoxication may impair the therapeutic effectiveness of amoxicillin.     

Pharmacokinetics of Pefloxacin in Goats after Intravenous or Oral Administration

The plasma concentrations and pharmacokinetics of the fluoroquinolone antimicrobial agent pefloxacin, following the administration of a single intravenous (10 mg/kg) or oral (20 mg/kg) dose, were investigated in healthy female goats. The antimicrobial activity in plasma was measured at predetermined times after drug administration by an agar well diffusion microbiological assay, using Escherichia coli (ATCC 25922) as the test organism. Concentrations of the drug 0.25 g/ml were maintained in plasma for up to 6 and 10 h after intravenous (IV) or oral administration of pefloxacin, respectively. The concentration–time data for pefloxacin in plasma after IV or oral administration conformed to two- and one-compartment open models, respectively. Plasma pefloxacin concentrations decreased rapidly during the initial phase after IV injection, with a distribution half-life (t _1/2 ) of 0.10±0.01 h. The terminal phase had a half-life (t _1/2 ) of 1.12±0.21 h. The volume of distribution at steady state (V _dss), mean residence time (MRT) and total systemic clearance (Cl_B) of pefloxacin were 1.08±0.09 L/kg, 1.39±0.23 h and 821±88 (ml/h)/kg, respectively. Following oral administration of pefloxacin, the maximum concentration in the plasma (C _max) was 2.22±0.48 g/ml and the interval from administration until maximum concentration (t _max) was 2.3±0.7 h. The absorption half-life (t _{1/2 ka}), mean absorption time (MAT) and elimination half-life of pefloxacin were 0.82±0.40, 4.2±1.0 and 2.91±0.50 h, respectively. The oral bioavailability of pefloxacin was 42%±5.8%. On the basis of the pharmacokinetic data, a dosage regimen of 20 mg/kg, IV at 8 h intervals or orally twice daily, is suggested for treating infections caused by drug-sensitive pathogens in goats.     

Pharmacokinetics, metabolism, and renal clearance of sulfadiazine, sulfamerazine, and sulfamethazine and of their N4-acetyl and hydroxy metabolites in calves and cows

The effect of molecular structure on the drug disposition and protein binding in plasma and milk, the urinary recovery, and the renal clearance of sulfadiazine, sulfamerazine, and sulfamethazine and of their N4-acetyl and hydroxy derivatives were studied in calves and cows. Sulfadiazine was highly acetylated and was slightly hydroxylated. Sulfamerazine and sulfamethazine were hydroxylated predominantly at the methyl group of the pyrimidine side chain; hydroxylation of the pyrimidine ring itself was more extensive for sulfamethazine than for sulfamerazine. At dosages between 100 and 200 mg/kg of body weight, sulfamethazine had a capacity-limited elimination pattern, which was not observed for sulfadiazine or sulfamerazine. The concentrations of the parent sulfonamide and its metabolites in plasma and milk were parallel, the latter being lower. Metabolite concentrations in milk were at least 8 times lower than those of the parent drug. Metabolism speeds drug elimination, producing compounds with renal clearance values higher than those of the parent drug. The effect on the metabolism and renal clearance of methyl substitution in the pyrimidine side chain is discussed.     

The impact of acute phase response on the plasma clearance of antipyrine, theophylline, phenytoin and nifedipine in rabbits

The impact of acute phase response (APR) on the plasma clearances of antipyrine, theophylline, phenytoin and nifedipine was studied using 50 female rabbits. APR was induced by a bolus intramuscular injection of Escherichia coli lipopolysaccharide (LPS, 50 microg/kg). No abnormal findings, other than an increase in rectal body temperature and the plasma concentration of interleukin-6 (IL-6), were observed in the LPS-treated animals. Twenty-four hours after LPS injection, the pharmacokinetic parameters of the four drugs were obtained following intravenous administrations of antipyrine (7 mg/kg), theophylline (5 mg/kg), phenytoin (10 mg/kg) and nifedipine (1 mg/kg). Total body clearances of antipyrine, theophylline, phenytoin and nifedipine in LPS-treated rabbits decreased, and terminal elimination half-life and the mean residence time of these drugs increased compared with those in the control rabbits. The apparent volume of distribution for phenytoin and nifedipine increased after the LPS injection, although the binding percentage of the drugs with plasma protein did not change. These results suggested that APR appears to decrease the plasma clearances of these drugs in rabbits, which may be due to the suppression of the activity of cytochrome P450 enzymes.     

Pharmacokinetics of sulfamethoxazole and trimethoprim in donkeys, mules, and horses

OBJECTIVE: To compare serum disposition of sulfamethoxazole and trimethoprim after IV administration to donkeys, mules, and horses. ANIMALS: 5 donkeys, 5 mules, and 3 horses. PROCEDURE: Blood samples were collected before (time 0) and 5, 15, 30, and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 24 hours after IV administration of sulfamethoxazole (12.5 mg/kg) and trimethoprim (2.5 mg/kg). Serum was analyzed in triplicate with high-performance liquid chromatography for determination of sulfamethoxazole and trimethoprim concentrations. Serum concentration-time curve for each animal was analyzed separately to estimate noncompartmental pharmacokinetic variables. RESULTS: Clearance of trimethoprim and sulfamethoxazole in donkeys was significantly faster than in mules or horses. In donkeys, mean residence time (MRT) of sulfamethoxazole (2.5 hours) was less than half the MRT in mules (6.2 hours); MRT of trimethoprim in donkeys (0.8 hours) was half that in horses (1.5 hours). Volume of distribution at steady state (Vdss) for sulfamethoxazole did not differ, but Vdss of trimethoprim was significantly greater in horses than mules or donkeys. Area under the curve for sulfamethoxazole and trimethoprim was higher in mules than in horses or donkeys. CONCLUSIONS AND CLINICAL RELEVANCE: Dosing intervals for IV administration of trimethoprim-sulfamethoxazole in horses may not be appropriate for use in donkeys or mules. Donkeys eliminate the drugs rapidly, compared with horses. Ratios of trimethoprim and sulfamethoxazole optimum for antibacterial activity are maintained for only a short duration in horses, donkeys, and mules.     

Pharmacokinetics and dosage of chlorpromazine in goats

Pharmacokinetic parameters which describe the distribution and elimination of chlorpromazine in goats were determined. Following the intravenous administration of a single dose (2.5 mg/kg), disposition of the drug was described in terms of the biexponential expression C _p= Ae^-αt+ Be^-βt. Based on total (free and bound) chlorpromazine levels in plasma, pseudo-distribution equilibrium was rapidly attained, and the elimination half-life was 1.51 ± 0.48 h (mean ± SD, n = 8). Total body clearance, which is the sum of all clearance processes, was 80 ± 25 ml/min/kg. The curves of an animal representative of the group, based on individual rate constants associated with the two-compartment open model, showed that at 5 h after drug administration 8% and 6% of the dose were present in the peripheral and central compartments, respectively. The kinetic parameters of chlorpromazine determined at a dosage level of 10 mg/kg body weight in six goats showed that the drug followed first-order kinetics and kinetic parameters were similar after both dose levels. Based on these findings and therapeutic plasma levels, a satisfactory intravenous regimen should be 2.0 – 3.5 mg/kg and the drug action will persist for 5–6 h.     

Bioavailability of morphine,methadone, hydromorphone,and oxymorphone following buccal administration in cats

Buccal administration of buprenorphine is commonly used to treat pain in cats. It has been argued that absorption of buprenorphine through the buccal mucosa is high, in part due to its pKa of 8.24. Morphine, methadone, hydromorphone, and oxymorphone have a pKa between 8 and 9. This study characterized the bioavailability of these drugs following buccal administration to cats. Six healthy adult female spayed cats were used. Buccal pH was measured prior to drug administration. Morphine sulfate, 0.2 mg/kg IV or 0.5 mg/kg buccal; methadone hydrochloride, 0.3 mg/kg IV or 0.75 mg/kg buccal; hydromorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal; or oxymorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal were administered. All cats received all treatments. Arterial blood was sampled immediately prior to drug administration and at various times up to 8 h thereafter. Bioavailability was calculated as the ratio of the area under the time–concentration curve following buccal administration to that following IV administration, each indexed to the administered dose. Mean ± SE (range) bioavailability was 36.6 ± 5.2 (12.7–49.5), 44.2 ± 7.9 (18.7–70.5), 22.4 ± 6.9 (6.4–43.4), and 18.8 ± 2.0 (12.9–23.5)% for buccal administration of morphine, methadone, hydromorphone, and oxymorphone, respectively. Bioavailability of methadone was significantly higher than that of oxymorphone.     

Elimination of sulfamethazine from edible tissues, blood, urine, and feces of turkey poults.

Sulfamethazine was administered to 8- to 10-week-old turkey poults intravenously (IV) at the dose level of 71.5 mg/kg of body weight, orally at the dose level of 143 mg/kg of body weight, or in the drinking water at the concentration of 0.1% over a 6-day period. The concentrations of free sulfamethazine in blood, muscle, skin, kidney, and liver were determined and semilogarithmic plots of concentration vs time for the various tissues indicated that the curve had a linear portion within the first 72-hour period of drug withdrawal. The rates of disappearance of sulfamethazine from the various tissues were proportional to the concentration in the tissues. After 72 hours of withdrawal and for as long as 14 days, sulfamethazine concentrations in kidney, liver, and skin of turkeys given the drug in the drinking water fluctuated between 0.1 and 0.4 ppm. Only 8.6% of the oral dose (143 mg/kg) and 16.5 to 17% of the IV dose (71.5 mg/kg) were recovered in urine and feces as the parent compound during the initial 72-hour period.     

Pharmacokinetics of clomipramine in dogs following single-dose intravenous and oral administration

OBJECTIVE: To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose. ANIMALS: 6 male and 6 female Beagles. PROCEDURES: Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method. RESULTS: Time to peak plasma concentrations of clomipramine and desmethylclomipramine following oral administration was 1.2 hours. For clomipramine, after IV administration, elimination half-life was 5 hours, mean residence time was 3 hours, and plasma clearance was 1.4 L/h/kg. Values for mean residence time and terminal half-life following oral administration were similar to values obtained following IV administration, and systemic bioavailability was approximately 20% for clomipramine and 140% for desmethylclomipramine, indicating fast absorption of clomipramine from the gastrointestinal tract and extensive first-pass metabolism. Administration of clomipramine with food did not alter the area under the concentration versus time curve for desmethylclomipramine but resulted in a 25% increase for clomipramine. Clomipramine and desmethylclomipramine were extensively bound (> 96%) to serum proteins. There were no significant differences in area under the concentration versus time curve between male and female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that there should not be any clinically important differences in efficacy regardless of whether clomipramine is administered with or without food.     

Effects of dexamethasone, levamisole, and dexamethasone-levamisole combination on neutrophil function in female goats

Effects of dexamethasone, levamisole, or combined dexamethasone-levamisole administration on polymorphonuclear neutrophil (PMN) function in healthy, adult female goats were studied. Goats were assigned to treated (n = 6) and control (n = 6) groups. In experiment 1, treated goats were given levamisole (6 mg/kg of body weight, IM). In experiment 2, treated goats were given 0.1 mg of dexamethasone/kg, IV, for 3 consecutive days, 1 mg of dexamethasone/kg, IV, for 6 consecutive days, and 6 mg of levamisole/kg, IM, with a 4th injection of 1 mg of dexamethasone/kg. All injections were administered 12 hours before blood collection. The PMN were evaluated for random migration and chemotaxis under agarose, ingestion of Staphylococcus aureus, cytochrome C reduction, iodination, and antibody-dependent cell-mediated cytotoxicity. Levamisole alone did not alter the function of caprine PMN. Both doses of dexamethasone caused increased random migration and decreased cytochrome C reduction and iodination. Dexamethasone resulted in no changes in chemotaxis, S aureus ingestion, and antibody-dependent cell-mediated cytotoxicity. Random migration and cytochrome C reduction returned toward base line in cells from dexamethasone and levamisole-treated goats. Although iodination activity in cells from dexamethasone-treated goats remained significantly (P less than 0.05) lower than those of controls after levamisole administration, a rebound toward base-line activity occurred.