Pharmacokinetics, urinary excretion and dosage regimen of diminazene in crossbred calves

The pharmacokinetics, urinary excretion and dosage regimen of diminazene were investigated in crossbred male calves following a single intramuscular dose (3.5 mg x kg-1). Following intramuscular administration, the pharmacokinetics of diminazene was described with a one-compartment open model. The absorption rate constant and absorption half-life were 9.86 +/- 3.06 h-1 and 0.121 +/- 0.40 h, respectively. The value of elimination half-life was 107.5 +/- 8.50 h. The apparent volume of distribution was 0.74 +/- 0.07 L x kg-1. Systemic availability following intramuscular administration was 91.7%. Approximately 65% of the administered dose of diminazene was eliminated in the urine within 24 h of its intramuscular administration. Diminazene was bound to plasma proteins to the extent of approximately 32%. The satisfactory intramuscular dosage regimen of diminazene for calves would be 2.24 mg x kg-1 followed by 1.5 mg x kg-1 at 7 days.     

Pharmacokinetics of diminazene in female Boran (Bos indicus) cattle

The disposition kinetics and bioavailability of diminazene in five healthy heifers were determined after single intravenous (i.v.) and intramuscular (i.m.) administration of the drug in sequence with a wash-out period between administrations of 6 weeks. Intact diminazene in plasma, whole blood and urine samples was analysed using high-performance liquid chromatography. Nonlinear regression analysis of the i.v. and i.m. data indicated that, for either route, the plasma disappearance curves of diminazene were best described by triexponential equations. The i.v. bolus was followed by rapid and biphasic distribution with half-life values of 0.04 h and 0.58 h, V_d(_ss) was 1.91 ± 0.42 1/kg, elimination half-life was 31.71 h while CI averaged 1.74 ± 0.40 ml/min/kg. Within 30 min of the i.v. dose, the erythrocyte/plasma partition ratio of diminazene was 0.30 ± 0.15. Diminazene was rapidly absorbed following i.m. administration; t _½k_a was 0.60 h. C_max, 4.68 ± 1.12 μg/ml, was attained in 10–15 min and systemic availability was 102.42 ± 7.25%. The half-life of the terminal disappearance phase was 145.48 h. About 8.26% of the i.m. dose was excreted intact in the urine within the first 24 h of treatment. In vitro , diminazene was bound to bovine plasma albumin to the extent of 38.01–91.10%.     

Pharmacokinetics and intramuscular bioavailability of amikacin in chickens following single and multiple dosing

The pharmacokinetics of amikacin were studied in healthy mature female chickens (n = 6). Single doses of amikacin were injected as an i.v. bolus (10 mg/kg) and i.m. (20 mg/kg) into the same birds with a 30-day rest period between treatments. Amikacin was determined by the fluorescence polarization immunoassay method. The i.v. pharmacokinetics could be described by a two-compartment model with a t1/2 alpha of 0.150 +/- 0.064 h and a t1/2 beta of 1.44 +/- 0.34 h. The total body clearance was 0.109 +/- 0.017 1/h/kg and the volume of distribution at steady-state was 0.193 +/- 0.060 l/kg. Following a single i.m. injection, the peak plasma concentration (Cmax) was 50.79 +/- 4.05 micrograms/ml and occurred at 0.50 +/- 0.26 h. The i.m. extent of absorption was 91.2 +/- 17.6%. Simultaneous modeling of i.v. and i.m. results provided estimates of an absorption half-life of 0.480 +/- 0.158 h. The i.m. pharmacokinetics after repeated administration were studied following the tenth dose (20 mg/kg, every 8 h). The Cssmax was 38.58 +/- 6.96 micrograms/ml and occurred at 0.79 +/- 0.37 h, and the biological half-life of amikacin was 1.86 +/- 0.47 h. The multiple dosing yielded peak concentrations of 39 micrograms/ml and trough concentrations of 3.26 micrograms/ml. Based on these data, the recommended amikacin dosage in chickens is 20 mg/kg body weight every 8 h.     

Pharmacokinetics of azithromycin after i.v. and i.m. administration to sheep

The pharmacokinetics (PK) of azithromycin after i.v. and i.m. injection at a single dosage of 20 mg/kg bodyweight was studied in sheep. Blood samples were collected from the jugular vein until 120 h after dosing for both routes. Plasma concentrations of azithromycin were determined by bioassay. The plasma concentration-time data of azithromycin best fitted a three-compartment model after i.v. administration and a two-compartment model with first-order absorption after i.m. administration. The elimination half-life (t(1/2lambdaz)) was 47.70 +/- 7.49 h after i.v. administration and 61.29 +/- 13.86 h after i.m. administration. Clearance value after i.v. dosing was 0.52 +/- 0.08 L/kg.h. After i.m. administration a peak azithromycin concentration (C(max)) of 1.26 +/- 0.19 mg/L was achieved at 1.24 +/- 0.31 h (t(max)). Area under the curve (AUC) were 38.85 +/- 5.83 mg.h/L and 36.03 +/- 1.52 mg.h/L after i.v. and i.m. administration respectively. Bioavailability obtained after i.m. administration was 94.08 +/- 11.56%. The high tolerability of this i.m. preparation and the favourable PK behaviour such as the long half-life and high bioavailability make azithromycin likely to be effective in sheep.     

Pharmacokinetics and therapeutic efficacy of rimantadine in horses experimentally infected with influenza virus A2.

OBJECTIVE: To determine pharmacokinetics of single and multiple doses of rimantadine hydrochloride in horses and to evaluate prophylactic efficacy of rimantadine in influenza virus-infected horses. ANIMALS: 5 clinically normal horses and 8 horses seronegative to influenza A. PROCEDURE: Horses were given rimantadine (7 mg/kg of body weight, i.v., once; 15 mg/kg, p.o., once; 30 mg/kg, p.o., once; and 30 mg/kg, p.o., q 12 h for 4 days) to determine disposition kinetics. Efficacy in induced infections was determined in horses seronegative to influenza virus A2. Rimantadine was administered (30 mg/kg, p.o., q 12 h for 7 days) beginning 12 hours before challenge-exposure to the virus. RESULTS: Estimated mean peak plasma concentration of rimantadine after i.v. administration was 2.0 micrograms/ml, volume of distribution (mean +/- SD) at steady-state (Vdss) was 7.1 +/- 1.7 L/kg, plasma clearance after i.v. administration was 51 +/- 7 ml/min/kg, and beta-phase half-life was 2.0 +/- 0.4 hours. Oral administration of 15 mg of rimantadine/kg yielded peak plasma concentrations of < 50 ng/ml after 3 hours; a single oral administration of 30 mg/kg yielded mean peak plasma concentrations of 500 ng/ml with mean bioavailability (F) of 25%, beta-phase half-life of 2.2 +/- 0.3 hours, and clearance of 340 +/- 255 ml/min/kg. Multiple doses of rimantadine provided steady-state concentrations in plasma with peak and trough concentrations (mean +/- SEM) of 811 +/- 97 and 161 +/- 12 ng/ml, respectively. Rimantadine used prophylactically for induced influenza virus A2 infection was associated with significant decreases in rectal temperature and lung sounds. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of rimantadine to horses can safely ameliorate clinical signs of influenza virus infection.     

Pharmacokinetics of cefepime administered by i.v. and i.m. routes to ewes

The pharmacokinetics of cefepime were studied following i.v. and i.m. administration of 20 mg/kg in 10 ewes. Following i.v. administration of a single dose, the plasma concentration-time curves of cefepime were best fitted using a two-compartment open model. The elimination half-life (t(1/2beta)) was 1.76 +/- 0.07 h, volume of distribution at steady-state [V(d(ss))] was 0.32 +/- 0.01 L/kg and total body clearance (Cl(B)) was 2.37 +/- 0.05 mL/min.kg. Following i.m. administration, the drug was rapidly absorbed with an absorption half-life (t(1/2ab)) of 0.49 +/- 0.05 h, maximum plasma concentration (Cmax) of 31.9 +/- 1.5 mug/mL was attained at (tmax) 1.1 +/- 0.2 h and the drug was eliminated with an elimination half-life (t(1/2el)) of 2.06 +/- 0.11 h. The systemic bioavailability (F) after i.m. administration of cefepime was 86.8 +/- 7.5%. The extent of plasma protein binding measured in vitro was 14.8 +/- 0.54%. The drug was detected in urine for 36 h postadministration by both routes.     

Acyclovir (Zovirax®) pharmacokinetics in Quaker parakeets, Myiopsitta monachus

The pharmacokinetics of intravenous (i.v.) and intramuscular (i.m.) single-dose administration of acyclovir were determined in Quaker parakeets. After i.v. injection at a dose of 20 mg/kg of acyclovir, elimination half-life was estimated at 0.65 h, volume of distribution at steady state was 627.65 ml/kg, and clearance was 11.22 ml/kg/min. The estimated pharmacokinetic values after i.m. injection at a dose of 40 mg/kg of acyclovir were an elimination half-life of 0.71 h and a bioavailability of 90.1%. The peak plasma acyclovir concentration occurred at 15 min when the drug was administered i.m. Plasma concentrations of acyclovir were undetectable 4-6 h after i.v. administration and 6-8 h after i.m. administration. Oral (capsules) and intravenous (sodium salt) formulations of acyclovir were given by gavage at 80 mg/kg. Peak concentrations with the sodium salt formulation were lower and developed more slowly than with the capsules. In studies designed to detect excessive drug accumulation or adverse side effects, acyclovir was administered i.m. at 40 mg/kg every 8 h for 7 days. Plasma concentrations were determined 15 min after (peak) and just prior to drug administration (trough). In another study acyclovir was gavaged at a dose of 80 mg/kg every 8 h for 4 days. Acyclovir plasma concentrations were determined just prior to and 2 h after drug administration. In both experiments, the birds maintained normal appetite and weight and did not exhibit excessive drug accumulation. Acyclovir plasma concentrations ranging from 2.07 +/- 1.09 micrograms/ml to 3.93 +/- 1.13 micrograms/ml were maintained for 4 days when acyclovir was administered in the feed and water (sole source of food and water).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative pharmacokinetics of marbofloxacin in healthy and Mannheimia haemolytica infected calves

The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance.     

Pharmacokinetics of intramuscular ketamine in young ostriches premedicated with romifidine

Ketamine is a short-acting dissociative anaesthetic for chemical restraint and surgical anaesthesia in domestic and non-domestic animals. The present study was designed to determine the pharmacokinetics of a single dose of ketamine (10 mg/kg) after intramuscular (i.m.) administration to young ostriches premedicated with romifidine. Ketamine was rapidly absorbed after i.m. administration. Maximal ketamine concentration (C(max)) of 2.93 +/- 0.61 microg/ml was reached at 12.5 +/- 2.50 min and thereafter ketamine concentrations decreased rapidly. The elimination half-life (t(1/2 z)) obtained was 62.37 +/- 17.37 min and mean residence time (MRT) was 77.33 +/- 19.12 min. The area under the curve (AUC) was 114.19 +/- 15.76 microg x min/ml.     

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.     

Pharmacokinetic parameters of ceftriaxone after single intravenous and intramuscular administration in camels (Camelus Dromedarius)

The purpose of this study was to investigate the plasma disposition kinetics of ceftriaxone in female camels (n=5) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injections at a dosage of 10mg kg(-1) body weight in all animals. A crossover design was carried out in two phases separated by 15 days. Jugular blood samples were collected serially for 48h and the plasma was analysed by high-performance liquid chromatography (HPLC). Following single i.v. injections the plasma concentration time curves of ceftriaxone were best fitted to a two-compartment model. The drug was rapidly distributed with half-life of distribution t(1/2alpha) of 0.24+/-0.01h and moderately eliminated with elimination rate constant and elimination half-life of 0.27+/-0.13h(-1) and 2.57+/-0.52h, respectively. The volume of distribution at steady state (V(dss)) was 0.32+/-0.01lkg(-1) and the total body clearance (Cl(tot)) was 0.11+/-0.01lkg(-1)h(-1), respectively. Following i.m. administration, the mean T(max), C(max), t(1/2el) and AUC values for plasma data were 1.03+/-0.23h, 21.54+/-2.61microg ml(-1), 1.76+/-0.03h and 85.82+/-11.21microg ml(-1)h(-1), respectively. The i.m. bioavailability was 93.42+/-21.4% and the binding percentage of ceftriaxone to plasma protein was moderate, ranging from 33% to 42% with an average of 34.5%.     

Pharmacokinetic disposition of a long-acting oxytetracycline formulation after single-dose intravenous and intramuscular administrations in the American alligator (Alligator mississippiensis).

The pharmacokinetics of a long-acting oxytetracycline preparation administered i.v. and i.m. to American alligators (Alligator mississippiensis) at 10 mg/kg was determined. Plasma levels of oxytetracycline were measured using high-performance liquid chromatography, and the resulting concentration versus time curve was analyzed using compartmental modeling and noncompartmental modeling techniques for i.v. and i.m. samples, respectively. A two-compartment model best represented the i.v. data. Intravenous administration of oxytetracycline resulted in an extrapolated mean plasma concentration at time zero of 60.63 +/- 28.26 microg/ml, with average plasma drug levels of 2.82 +/- 0.71 microg/ml at the end of the 192-hr sampling period. Plasma volume of distribution for i.v. oxytetracycline was 0.20 +/- 0.09 L/kg, with a harmonic mean elimination half-life of 15.15 hr and mean total body clearance rate of 0.007 +/- 0.002 L/hr/kg. Intramuscular administration of oxytetracycline achieved a mean peak plasma concentration of 6.85 +/- 1.96 microg/ml at 1 hr after administration, with average plasma drug levels of 4.96 +/- 1.97 microg/ml at the end of the 192-hr sampling period. The harmonic mean terminal elimination half-life for i.m. oxytetracycline was 131.23 hr. Based on the results of this study, long-acting preparations of oxytetracycline administered parenterally to American alligators at 10 mg/kg q 5 days is expected to maintain plasma concentrations above the minimum inhibitory concentration of 4.0 microg/ml for susceptible organisms.     

Pharmacokinetic variables and tissue residues of enrofloxacin and ciprofloxacin in healthy pigs

OBJECTIVES: To determine pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after a single i.v. and i.m. administration of enrofloxacin and tissue residues after serial daily i.m. administration of enrofloxacin in pigs. ANIMALS: 20 healthy male pigs. PROCEDURE: 8 pigs were used in a crossover design to investigate pharmacokinetics of enrofloxacin after a single i.v. and i.m. administration (2.5 mg/kg of body weight). Twelve pigs were used to study tissue residues; they were given daily doses of enrofloxacin (2.5 mg/kg, i.m. for 3 days). Plasma and tissue concentrations of enrofloxacin and ciprofloxacin were determined. Residues of enrofloxacin and ciprofloxacin were measured in fat, kidney, liver, and muscle. RESULTS: Mean (+/-SD) elimination half-life and mean residence time of enrofloxacin in plasma were 9.64+/-1.49 and 12.77+/-2.15 hours, respectively, after i.v. administration and 12.06+/-0.68 and 17.15+/-1.04 hours, respectively, after i.m. administration. Half-life at alpha phase of enrofloxacin was 0.23+/-0.05 and 1.94+/-0.70 hours for i.v. and i.m. administration, respectively. Maximal plasma concentration was 1.17 +/-0.23 microg/ml, and interval from injection until maximum concentration was 1.81+/-0.23 hours. Renal and hepatic concentrations of enrofloxacin (0.012 to 0.017 microg/g) persisted for 10 days; however, at that time, ciprofloxacin residues were not detected in other tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered i.m. at a dosage of 2.5 mg/kg for 3 successive days, with a withdrawal time of 10 days, resulted in a sum of concentrations of enrofloxacin and ciprofloxacin that were less than the European Union maximal residue limit of 30 ng/g in edible tissues.     

Pharmacokinetics of florfenicol and its major metabolite, florfenicol amine, in rabbits

The pharmacokinetics of florfenicol and its active metabolite florfenicol amine were investigated in rabbits after a single intravenous (i.v.) and oral (p.o.) administration of florfenicol at 20 mg/kg bodyweight. The plasma concentrations of florfenicol and florfenicol amine were determined simultaneously by an LC/MS method. After i.v. injection, the terminal half-life (t(1/2lambdaz)), steady-state volume of distribution, total body clearance and mean residence time of florfenicol were 0.90 +/- 0.20 h, 0.94 +/- 0.19 L/kg, 0.63 +/- 0.06 L/h/kg and 1.50 +/- 0.34 h respectively. The peak concentrations (C(max)) of florfenicol (7.96 +/- 2.75 microg/mL) after p.o. administration were observed at 0.90 +/- 0.38 h. The t(1/2lambdaz) and p.o. bioavailability of florfenicol were 1.42 +/- 0.56 h and 76.23 +/- 12.02% respectively. Florfenicol amine was detected in all rabbits after i.v. and p.o. administration. After i.v. and p.o. administration of florfenicol, the observed Cmax values of florfenicol amine (5.06 +/- 1.79 and 3.38 +/- 0.97 microg/mL) were reached at 0.88 +/- 0.78 and 2.10 +/- 1.08 h respectively. Florfenicol amine was eliminated with an elimination half-life of 1.84 +/- 0.17 and 2.35 +/- 0.94 h after i.v. and p.o. administration respectively.     

Pharmacokinetics and pharmacodynamics of butorphanol in llamas after intravenous and intramuscular administration.

OBJECTIVE: To evaluate disposition of butorphanol after i.v. and i.m. administration, effects on physiologic variables, and analgesic efficacy after i.m. administration in llamas. DESIGN: Nonrandomized crossover study. ANIMALS: 6 healthy adult male llamas. PROCEDURE: Butorphanol (0.1 mg/kg [0.045 mg/lb] of body weight) was administered i.m. first and i.v. 1 month later. Blood samples were collected intermittently for 24 hours after administration. Plasma butorphanol versus time curves were subjected to pharmacokinetic analysis. Two months later, butorphanol (0.1 mg/kg) was administered i.m., and physiologic variables and analgesia were assessed. RESULTS: Extrapolated peak plasma concentrations after i.v. and i.m. administration were 94.8 +/- 53.1 and 34.3 +/- 11.6 ng/ml, respectively. Volume of distribution at steady state after i.v. administration was 0.822 +/- 0.329 L/kg per minute and systemic clearance was 0.050 +/- 0.014 L/kg per minute. Slope of the elimination phase was significantly different, and elimination half-life was significantly shorter after i.v. (15.9 +/- 9.1 minutes) versus i.m. (66.8 +/- 13.5 minutes) administration. Bioavailability was 110 +/- 49% after i.m. administration. Heart rate decreased and rectal temperature increased. Somatic analgesia was increased for various periods. Two llamas became transiently sedated, and 2 became transiently excited after butorphanol administration. CONCLUSIONS AND CLINICAL RELEVANCE: Although i.v. administration of butorphanol results in a short half-life that may limit its analgesic usefulness, the elimination half-life of butorphanol administered i.m. is likely to be clinically useful. The relationship among plasma butorphanol concentration, time, and analgesia differed with the somatic analgesia model; clinically useful analgesia may occur at lower plasma concentrations than those reported here.     

Prednisolone succinate and prednisolone acetate in cattle: pharmacokinetics and action on the adrenal gland

The pharmacokinetics of prednisolone were studied in a group of 6 cows given prednisolone 21-sodium succinate IV and IM (600 micrograms/kg of body weight expressed as prednisolone alcohol) and prednisolone acetate IM (600 micrograms/kg of body weight expressed as prednisolone alcohol). After IV administration of prednisolone 21-sodium succinate, the half-life of elimination was 3.6 +/- 1.177 hours. After IM administration of prednisolone 21-sodium succinate, absorption was rapid and complete. After IM administration of prednisolone acetate, absorption was very slow with an absorption half-life of 48 hours, but was still complete. Basal plasma hydrocortisone was about 7.5 ng/ml. After IV and IM administration of prednisolone 21-sodium succinate, plasma hydrocortisone returned to normal values within 48 hours. In contrast, after IM administration of prednisolone acetate, a long adrenal suppression lasting from 4 to 6 weeks was observed.     

Plasma profiles of ivermectin in horses following oral or intramuscular administration

A study was undertaken in order to evaluate and compare ivermectin's (IVM) plasma disposition kinetic parameters after oral or intramuscular (IM) administration in horses. Ten clinically healthy adult horses, weighing 380-496 kg body weight (BW), were allocated to two experimental groups of five horses. Group I, was treated with an oral paste formulation of IVM at the manufacturer's recommended dose of 0.2 mg/kg BW. Group II, was treated IM with an injectable 1% formulation of IVM at a dose of 0.2 mg/kg BW. Blood samples were collected by jugular puncture at different times between 0.5 h and 75 days post-treatment. After plasma extraction and derivatization, samples were analysed by high-performance liquid chromatography with fluorescence detection. A computerized kinetic analysis was performed, and data were compared using the Wilcoxon signed rank test. The parent molecule was detected in plasma between 30 min and either 20 (oral) or 40 (IM) days post-treatment. Significant differences were found for the time corresponding to peak plasma concentrations (tmax) and for absorption half-life. Peak plasma concentrations (Cmax) of 51.3 +/- 16.1 ng/ml (mean +/- SD) were obtained after oral administration and of 31.4 +/- 6.0 ng/ml for the IM route. The values for area under concentration-time curve were 137.1 +/- 35.9 ng day/ml for the group treated orally, and 303.2 +/- 4.3 ng day/ml for the IM treated group. The mean plasma residence times were 4.2 +/- 0.4 and 8.9 +/- 0.7 days for oral and IM-treated groups, respectively. The results of this study show that the route of administration considerably affects the disposition of IVM. A significant difference in bioavailabilty and half-life of elimination of IVM was observed after IM administration compared with oral administration. A close relationship between pharmacokinetic profiles and the clinical efficacy of IVM was established.     

Disposition of clorazepate in dogs after single- and multiple-dose oral administration

Clorazepate dipotassium was administered orally to 8 healthy dogs at a dosage of 2 mg/kg of body weight, q 12 h, for 21 days. Serum disposition of nordiazepam, the principle metabolite of clorazepate, was determined after the first and last dose of clorazepate. Disposition variables were analyzed by use of model-independent pharmacokinetics by the predictive equations method and the trapezoidal rule method. Complete blood counts, serum chemical analyses, and urinalyses were performed before administration of clorazepate and at 10 and 21 days after administration of clorazepate. Maximal nordiazepam concentrations ranged from 446 to 1,542 ng/ml (814 +/- 334 ng/ml), at 59 to 180 minutes (97.9 +/- 42.0 minutes) after a single oral dose of clorazepate. Maximal nordiazepam concentrations ranged from 927 to 1,460 ng/ml (1,308 +/- 187.6 ng/ml), at 120 to 239 minutes (153 +/- 57.9 minutes) after multiple oral doses of clorazepate. Serum disposition was significantly altered after multiple doses of clorazepate. Using data determined by the predictive equations method, the mean residence time after multiple doses (712 +/- 214 minutes) was longer (P less than 0.05) than after a single dose (527 +/- 95.8 minutes). Oral volume of distribution after multiple doses of clorazepate (1.76 +/- 0.647 L/kg) was smaller (P less than 0.02) than after a single dose (3.18 +/- 1.52 L/kg). Oral clearance after multiple doses of clorazepate (3.09 +/- 0.726 ml/min/kg) was less (P less than 0.001) than after a single dose (6.54 +/- 2.15 ml/min/kg). Absorption half-life after multiple doses (72 minutes) was longer (P less than 0.01) than after a single dose (33 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of selamectin following intravenous,oral and topical administration in cats and dogs

The pharmacokinetics of selamectin were evaluated in cats and dogs, following intravenous (0.05, 0.1 and 0.2 mg/kg), topical (24 mg/kg) and oral (24 mg/kg) administration. Following selamectin administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). After intravenous administration of selamectin to cats and dogs, the mean maximum plasma concentrations and area under the concentration-time curve (AUC) were linearly related to the dose, and mean systemic clearance (Clb) and steady-state volume of distribution (Vd(ss)) were independent of dose. Plasma concentrations after intravenous administration declined polyexponentially in cats and biphasically in dogs, with mean terminal phase half-lives (t(1/2)) of approximately 69 h in cats and 14 h in dogs. In cats, overall Clb was 0.470 +/- 0.039 mL/min/kg (+/-SD) and overall Vd(ss) was 2.19 +/- 0.05 L/kg, compared with values of 1.18 +/- 0.31 mL/min/kg and 1.24 +/- 0.26 L/kg, respectively, in dogs. After topical administration, the mean C(max) in cats was 5513 +/- 2173 ng/mL reached at a time (T(max)) of 15 +/- 12 h postadministration; in dogs, C(max) was 86.5 +/- 34.0 ng/mL at T(max) of 72 +/- 48 h. Bioavailability was 74% in cats and 4.4% in dogs. Following oral administration to cats, mean C(max) was 11,929 +/- 5922 ng/mL at T(max) of 7 +/- 6 h and bioavailability was 109%. In dogs, mean C(max) was 7630 +/- 3140 ng/mL at T(max) of 8 +/- 5 h and bioavailability was 62%. There were no selamectin-related adverse effects and no sex differences in pharmacokinetic parameters. Linearity was established in cats and dogs for plasma concentrations up to 874 and 636 ng/mL, respectively. Pharmacokinetic evaluations for selamectin following intravenous administration indicated a slower elimination from the central compartment in cats than in dogs. This was reflected in slower clearance and longer t(1/2) in cats, probably as a result of species-related differences in metabolism and excretion. Inter-species differences in pharmacokinetic profiles were also observed following topical administration where differences in transdermal flux rates may have contributed to the overall differences in systemic bioavailability.     

Pharmacokinetics of tramadol and o-desmethyltramadol in goats after intravenous and oral administration

The aim of this trial was to implement a method to obtain a tool for analyses of tramadol and the main metabolite, o-desmethyltramadol (M1), in goat's plasma, and to evaluate the pharmacokinetics of these substances following intravenous (i.v.) and oral (p.o.) administration in female goats. The pharmacokinetics of tramadol and M1 were examined following i.v. or p.o. tramadol administration to six female goats (2 mg/kg). Average retention time was 5.13 min for tramadol and 2.42 min for M1. The calculated parameters for half-life, volume of distribution and total body clearance were 0.94+/-0.34 h, 2.48+/-0.58 L/kg and 2.18+/-0.23 L/kg/h following 2 mg/kg tramadol HCl administered intravenously. The systemic availability was 36.9+/-9.1% and half-life 2.67+/-0.54 h following tramadol 2 mg/kg p.o. M1 had a half-life of 2.89+/-0.43 h following i.v. administration of tramadol. Following p.o., M1 was not detectable.