Pharmacokinetics of pethidine administered intramuscularly and intravenously to dogs over 10 years old

The pharmacokinetics of pethidine administered postoperatively both intravenously and intramuscularly was investigated in dogs aged over 10 years. When the drug was given intravenously (2 mg kg-1), plasma levels declined in a biexponential manner, with an elimination half-life of 62.7 minutes. Following its intramuscular administration at the same dose rate, absorption was very slow and two distinct rates of absorption were observed. Maximum plasma concentrations were not achieved until 33 minutes after drug administration. The elimination of the intramuscularly administered drug was also slow with a t 1/2 beta' of 145.9 minutes. Thus, it seems that in elderly animals pethidine has a long elimination half-life and a slowed rate of absorption. However, the total body clearance of the drug does not seem to be affected by age.     

Pharmacokinetics of intravenously and intramuscularly administered ticarcillin and clavulanic acid in foals

Serum concentrations of ticarcillin and clavulanic acid were measured in healthy foals (2 to 6 months old) given the drugs in combination by intravenous and intramuscular routes of administration. Five foals were administered 50 mg of ticarcillin/kg of body weight and 1.67 mg of clavulanic acid/kg, IV. Five foals were administered 100 mg of ticarcillin/kg and 3.33 mg of clavulanic acid/kg, IV, and 4 of those 5 were given the same combined dose IM. The elimination half-life of ticarcillin for intravenous administration was 0.83 hour for the low dosage and 0.96 hour for the high dosage. After intramuscular administration, the half-life of elimination was 2.9 hours, with bioavailability of 54.6%. For IV administered clavulanic acid, the elimination half-life was 0.65 hour for the low dosage and 0.74 hour for the high dosage. After intramuscular administration, the elimination half-life was 0.92 hour, and bioavailability was 68.1%. A combined dosage, 50 mg of ticarcillin/kg and 1.67 mg of clavulanic acid/kg, given every 6 hours is recommended.     

Disposition kinetics of tylosin administered intravenously and intramuscularly to pigs

The distribution of tylosin was studied using a crossover design, in six pigs following i.v. and i.m. administration of 10 mgkg(-1) b.w. Plasma samples were analysed by HPLC and UV absorbance detection. After i.v. administration, t(1/2beta) was 271.3 min, V(d) 14.6 Lkg(-1), V(ss) 9.7 Lkg(-1) and CL 26.8 mLmin(-1)kg(-1). After i.m. administration, a C(max) of 1 microgmL(-1) was reached at 90 min. Mean absorption time was 1988.7 min and bioavailability was 95%.     

Pharmacokinetics and bioavailability of 2-mercaptopropionylglycine administered intravenously and orally in dogs

The pharmacokinetic disposition of 2-mercaptopropionylglycine (2-MPG) given as a single intravenous injection and/or as a single oral dose was studied in 9 normal and 13 cystinuric dogs. After intravenous injection of approximately 10 or 20 mg/kg body weight the pharmacokinetics were best described by a three-exponential function. The first phase involved a distribution process apparently including establishment of drug-plasma protein and drug-tissue binding. The second phase involved rapid renal elimination and 60% of the drug was excreted within 3 h of administration. There was also a slow terminal third phase with a long half-life after both intravenous (t1/2 = 23 h) and oral (t1/2 = 22 h) administration. No dose dependency was observed. A deep pool of reversibly tissue-bound 2-MPG was indicated by a Vss of 3.3 +/- 0.9 l/kg body weight and the long terminal elimination phase. Total clearance was estimated as 4.1 +/- 0.9 ml/min/kg body weight. 2-MPG was eliminated mainly by renal excretion, but there was a difference in recovery of dose between normal and cystinuric dogs. During the first 24 h after intravenous and oral administration, 69% and 54%, respectively, of the drug was recovered in the urine of normal dogs. The corresponding figures in cystinuric dogs were 44% and 29%, respectively. The absolute bioavailability (FAUC) was 88 +/- 20% in normal dogs.     

Pharmacokinetics of single doses of gentamicin given intravenously and intramuscularly to turkeys

The disposition and absorption kinetics of gentamicin were studied in healthy, mature male and female turkeys (n = 10). Single doses of gentamicin (5 mg/kg) were injected either i.v. or i.m. with a 30-day rest period between each treatment. Baseline and serial venous blood samples (n = 17) were collected from each turkey. Serum concentrations of gentamicin were determined in duplicate for 24 h after each treatment, using radio-immunoassay. Using nonlinear least-square regression methods, the combined data of the i.v. and i.m. treatments were best described by a two-compartment open model. Kinetic analysis of the data after a single i.v. dose provided the following mean values: t1/2 alpha = 0.170 +/- 0.093 h, t1/2 beta = 2.57 +/- 0.79 h, MRT = 3.62 +/- 0.96 h, Vc = 0.090 +/- 0.017 l/kg, Vd(ss) = 0.172 +/- 0.024 l/kg, Vd(area) = 0.190 +/- 0.030 l/kg, and Clt = 49.8 +/- 9.8 ml/h/kg. After a single i.m. dose, the following mean values were determined: MRT = 5.10 +/- 1.73 h, t1/2abs = 0.74 +/- 0.66 h, tlag = 0.07 +/- 0.19 h, Clt/F = 50.7 +/- 12.5 ml/h/kg, Vd(area)/F = 0.193 +/- 0.044 l/kg, and F = 102 +/- 21%. Kinetic calculations made with the single i.m. data predicted that an i.m. injection of gentamicin at the dosage rate of 3 mg/kg q. every 12 h would provide average steady state serum concentrations of 4.93 micrograms/ml.     

Comparison of quality of induction of anaesthesia between intramuscularly administered ketamine, intravenously administered ketamine and intravenously administered propofol in xylazine premedicated cats

The quality of induction of general anesthesia produced by ketamine and propofol, 2 of the most commonly used anaesthetic agents in cats, was assessed. Eighteen cats admitted for elective procedures were randomly assigned to 3 groups and then premedicated with xylazine 0.75 mg/kg intramuscularly before anaesthesia was induced with ketamine 15 mg/kg intramuscularly (KetIM group), ketamine 10 mg/kg intravenously (KetIV group) or propofol 4 mg/kg intravenously (PropIV group). Quality of induction of general anaesthesia was determined by scoring ease of intubation, degree of struggling, and vocalisation during the induction period. The quality of induction of anaesthesia of intramuscularly administered ketamine was inferior to that of intravenously administered ketamine, while intravenously administered propofol showed little difference in quality of induction from ketamine administered by both the intramuscular and intravenous routes. There were no significant differences between groups in the ease of intubation scores, while vocalisation and struggling were more common in cats that received ketamine intramuscularly than in those that received intravenously administered ketamine or propofol for induction of anaesthesia. Laryngospasms occurred in 2 cats that received propofol. The heart rates and respiratory rates decreased after xylazine premedication and either remained the same or decreased further after induction for all 3 groups, but remained within normal acceptable limits. This study indicates that the 3 regimens are associated with acceptable induction characteristics, but administration of ketamine intravenously is superior to its administration intramuscularly and laryngeal desensitisation is recommended to avoid laryngospasms.     

Pharmacokinetics of enrofloxacin administered intravenously and orally to foals

OBJECTIVE: To determine the pharmacokinetics of enrofloxacin administered IV and orally to foals. ANIMALS: 5 clinically normal foals. PROCEDURE: A 2-dose cross-over trial with IV and oral administration was performed. Enrofloxacin was administered once IV (5 mg/kg of body weight) to 1-week-old foals, followed by 1 oral administration (10 mg/kg) after a 7-day washout period. Blood samples were collected for 48 hours after the single dose IV and oral administrations and analyzed for plasma enrofloxacin and ciprofloxacin concentrations by use of high-performance liquid chromatography. RESULTS: For IV administration, mean +/- SD total area under the curve (AUC0-infinity) was 48.54 +/- 10.46 microg x h/ml, clearance was 103.72 +/- 0.06 ml/kg/h, half-life (t1/2beta) was 17.10 +/- 0.09 hours, and apparent volume of distribution was 2.49 +/- 0.43 L/kg. For oral administration, AUC0-infinity was 58.47 +/- 16.37 microg x h/ml, t1/2beta was 18.39 +/- 0.06 hours, maximum concentration (Cmax) was 2.12 +/- 00.51 microg/ml, time to Cmax was 2.20 +/- 2.17 hours, mean absorption time was 2.09 +/- 0.51 hours, and bioavailability was 42 +/- 0.42%. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with adult horses given 5 mg of enrofloxacin/kg IV, foals have higher AUC0-infinity, longer t1/2beta, and lower clearance. Concentration of ciprofloxacin was negligible. Using a target Cmax to minimum inhibitory concentration ratio of 1:8 to 1:10, computer modeling suggests that 2.5 to 10 mg of enrofloxacin/kg administered every 24 hours would be effective in foals, depending on minimum inhibitory concentration of the pathogen.     

Pharmacokinetics of single doses of digoxin administered intravenously to ducks, roosters, and turkeys

A single dose of digoxin was injected, IV, into 5 mature male turkeys (0.066 mg/kg of body weight), 8 male ducks (0.066 mg/kg), and 6 roosters (0.33 mg/kg). Twenty-three serial venous blood samples were collected before (baseline) and after the administration of digoxin to turkeys, ducks, and roosters. Plasma concentrations of digoxin were determined in duplicate by a radioimmunoassay that was validated for avian species. The plasma concentrations were best fitted by a 3 (turkeys, ducks)- and 2 (roosters)-compartment open model, with first-order elimination from the central compartment. Significant (P less than 0.05) kinetic differences were determined among species. Mean half-life (t1/2) for ducks, roosters, and turkeys were 8.30 +/- 2.70 (mean +/- SD), 6.67 +/- 3.50, and 23.7 +/- 4.8 hours, respectively. The volume of distribution at steady state (Vss) was 14.7 +/- 2.9, 3.13 +/- 0.49, and 2.27 +/- 0.36 L/kg, and total body clearance (CL) of drug was 1.54 +/- 0.43, 0.461 +/- 0.187, and 0.136 +/- 0.022 L/h/kg for ducks, roosters, and turkeys, respectively. The mean residence time was 10.3 +/- 3.9, 8.37 +/- 4.97, and 16.8 +/- 2.2 hours, respectively. Volume of distribution at steady state and CL in ducks were several fold higher than that in turkeys. The terminal half-life of digoxin determined for ducks and roosters in this study was considerably shorter than those previously reported for several mammalian species.     

Pharmacokinetics of sulphamethoxazole and trimethoprim administered intravenously and orally to Japanese quails

The pharmacokinetic behaviour of sulphamethoxazole and trimethoprim was studied after combined intravenous (i.v.) administration at doses of 20 mg/kg and 4 mg/kg, respectively, and after oral administration at doses of 50 mg/kg and 10 mg/kg. The serum concentration versus time data after i.v. administration were best described by the biexponential equations C = 34.77.e^-2.655.t+ 39.03.e^-0.241.t for sulphamethoxazole and C = 3.29.e^-3.878.t+ 0.83.e^-0.306.t for trimethoprim. Mean biological half-lives of the drugs were 2.89 ± 0.11 and 2.38 ± 0.33 h, respectively. The distribution volumes (V_area) were 0.475 ± 0.026 l/kg (sulphamethoxazole) and 3.89 ± 0.61 I/kg (trimethoprirn). Orally administered sulphamethoxazole and trimethoprim were rapidly absorbed. The maximum serum concentrations were reached 0.5-1 h after administration. The bioavailability was 8 1% for sulphamethoxazole and 41% for trimethoprim.     

Disposition kinetics of tylosin administered intravenously and intramuscularly in desert sheep and Nubian goats

The pharmacokinetic behaviour of tylosin was compared in five Desert sheep and five Nubian goats. The animals were given a single dose of 20% tylosin (15 mg/kg), either intravenously (i.v.) or intramuscularly (i.m.). Following i.v. administration, the volumes of distribution and the elimination half-life times were similar in both species, whereas in goats a greater volume of the central compartment and faster clearance were observed. For the i.m. route, similar pharmacokinetics were observed in both species. The bioavailability (f) of the drug in goats (0.84 +/- 0.11) was not significantly higher than that in sheep (0.73 +/- 0.08). The present study has shown that, despite the significant differences in some of the drug pharmacokinetic parameters between sheep and goats for the i.v. route, identical intravenous and intramuscular dosage regimens of tylosin may be recommended for the two species.     

Pharmacokinetics of intravenously and orally administered pyrimethamine in horses.

Single-dose pharmacokinetic variables of pyrimethamine were studied in horses. Pyrimethamine (1 mg/kg of body weight) was administered IV and orally to 6 adult horses, and plasma samples were obtained at frequent intervals thereafter. Plasma pyrimethamine concentration was assayed by gas chromatography, and concentration-time data were analyzed, using a pharmacokinetic computer program. The IV and oral administration data were best described by 3-compartment and 1-compartment models, respectively. The median volume of distribution at steady state after IV administration was 1,521 ml/kg and the median elimination half-time was 12.06 hours. Mean plasma concentration after oral administration fluctuated between a maximal concentration of 0.18 microgram/ml and 0.09 microgram/ml (24 hours after dosing). Bioavailability after oral administration was 56%.     

Effects of age on the pharmacokinetics of single dose ceftiofur sodium administered intramuscularly or intravenously to cattle

The effects of maturation on the intravenous (IV) and intramuscular (IM) pharmacokinetics of ceftiofur sodium following a dose of 2.2 mg ceftiofur equivalents/kg body weight were evaluated in 16 one-day-old Holstein bull calves (33-53 kg body weight initially; Group 1) and 14 six-month-old Holstein steers (217-276 kg body weight initially; Group 2). Group 1 calves were fed unmedicated milk replacer until 30 days of age and were then converted to the same roughage/concentrate diet as Group 2. Groups 1-IV and 2-IV received ceftiofur sodium IV, and Groups 1-IM and 2-IM received ceftiofur sodium IM. Group 1 calves were dosed at 7 days of age and at 1 and 3 months of age; group 2 calves were dosed at 6 and 9 months of age. Blood samples were obtained serially from each calf, and plasma samples were analysed using an HPLC assay that converts ceftiofur and all desfuroylceftiofur metabolites to desfuroylceftiofur acetamide. C_max values were similar in all calves, and were no higher in younger calves than in older calves. Plasma concentrations remained above 0.150 μg ceftiofur free acid equivalents/mL for 72 h in 7-day-old calves, but were less than 0.150 μg/mL within 48 h following IV or IM injection for 6- and 9-month-old calves. Intramuscular bioavailability, assessed by comparing the model-derived area under the curve (AUC_mod) from IM and IV injection at each age, appeared to be complete. After IV administration, the AUC_mod in 7-day-old and 1-month-old calves (126.92±21.1 μg-h/mL and 135.0±21.6 μg.h/mL, respectively) was significantly larger than in 3-, 6- and 9-month-old calves (74.0±10.7 μg.h/mL, 61.0±17.7 μg.h/mL and 68.5±12.8 μg.h/mL, respectively; P< 0.0001). The V_d(ss) decreased linearly within the first 3 months of life in cattle (0.345±0.0616 L/kg, 0.335±0.919 L/kg and 0.284±0.0490 L/kg, respectively; P= 0.031), indicative of the decreasing extracellular fluid volume in maturing cattle. The Cl_b was significantly smaller in 7-day-old and 1-month-old calves (0.0178±0.00325 L/h.kg and 0.0167±0.00310 L/h.kg, respectively) than in 3-, 6- and 9-month-old calves (0.0303±0.0046 L/h.kg, 0.0398±0.0149 L/h.kg and 0.0330±0.00552 L/h.kg, respectively; P≦0.001). This observation may be indicative of maturation of the metabolism and/or excretion processes for ceftiofur and desfuroylceftiofur metabolites. The approved dosage regimens for ceftiofur sodium of 1.1-2.2 mg/kg administered once daily for up to 5 consecutive days will provide plasma concentrations above the MIC for bovine respiratory disease pathogens for a longer period of time in neonatal calves than in older calves. Peak plasma concentrations of ceftiofur and desfuroylceftiofur metabolites were no higher in neonatal calves than in more mature cattle, highly suggestive that peak tissue concentrations would be no higher in neonatal calves than in more mature cattle.     

Urinary excretion by dogs of intravenously administered simple sugars

Seven simple sugars, commonly used in intestinal function tests, were simultaneously administered intravenously to dogs and their urinary excretion was measured to assess their potential for metabolic degradation. Lactose, lactulose and 3-O-methyl-D-glucose were excreted unchanged, but small proportions of palatinose and sucrose were not, and were assumed to have been metabolised. More than half of the administered D-xylose and a quarter of L-rhamnose was not excreted and was assumed to have been metabolised. These findings may be significant for the interpretation of differential sugar absorption tests and the D-xylose tolerance test.     

Dose response to butorphanol administered subcutaneously to increase visceral nociceptive threshold in dogs.

Butorphanol (0.025, 0.05, 0.1, 0.2, 0.4, and 0.8 mg/kg of body weight, and placebo) was given SC to 8 healthy unmedicated dogs to determine its efficacy for visceral analgesia, using a colonic balloon for minimal threshold nociceptor stimulation. Degree of sedation; systolic, diastolic, and mean arterial pressure; and pulse rate were recorded. The highest 3 dosages, 0.2, 0.4, and 0.8 mg/kg, were found to be most effective, with 0.8 mg/kg the only dosage that was significantly different from control responses at the 45-minute interval. Duration of analgesia ranged from 23 to 53 minutes for all 6 dosages and dosing durations were not significantly different from one another. Blood pressures did not change, but pulse rate was significantly decreased by 0.8 mg of butorphanol/kg. We concluded that butorphanol is an effective visceral analgesic of relatively short duration in the dog.     

Pharmacokinetics of ceftriaxone administered by the intravenous, intramuscular or subcutaneous routes to dogs

The purpose of this study was to investigate the pharmacokinetics of ceftriaxone after single intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) doses in healthy dogs. Six mongrel dogs received ceftriaxone (50 mg/kg) by each route in a three-way crossover design. Blood samples were collected in predetermined times after drug administration. Results are reported as mean +/- standard deviation (SD). Total body clearance (Cl(t)) and apparent volume of distribution (V(z)) for the i.v. route were 3.61 +/- 0.78 and 0.217 +/- 0.03 mL/kg, respectively. Terminal half-life harmonic mean (t(1/2 lambda)) was 0.88; 1.17 and 01.73 h for the i.v., i.m and s.c. routes, respectively. Mean peak serum concentration (C(max)) was 115.10 +/- 16.96 and 69.28 +/- 14.55 microg/mL for the i.m and s.c. routes, respectively. Time to reach C(max) (t(max)) was 0.54 +/- 0.24 and 1.29 +/- 00.64 h for the i.m and s.c. routes, respectively. Mean absorption time (MAT) was 1.02 +/- 0.64 and 2.23 +/- 00.73 h for the i.m and s.c. routes, respectively. Bioavailability was 102 +/- 27 and 106 +/- 14% for the i.m and s.c. routes, respectively. Statistically significant differences were determined in C(max), t(max), MAT and t(1/2 lambda) of s.c. administered ceftriaxone when compared with the i.v and i.m. routes. These findings suggest that once or twice s.c. or i.m. daily administered ceftriaxone should be adequate to treat most susceptible infections in dogs.     

Irritation, bioavailability, and residue aspects of ten oxytetracycline formulations administered intramuscularly to pigs

After intramuscular administration to pigs (dosage 20-35 mg/kg) great differences were found among 10 injectable oxytetracycline (OTC) formulations with respect to irritation and persistence at the injection site and to the residue state of edible tissues. The OTC recovery percentages at the injection site 7-10 days after injection ranged from less than 0.001 to 0.15 per cent for three 10 per cent-formulations and from 0.12 to 20.5 per cent for seven 20 per cent-formulations. The OTC recovery percentage was obvious related to the extent of tissue irritation at the injection site, which was particularly evident for the 20 per cent-formulations. Serious doubt is expressed about advantages of so-called 'long-acting' formulations.     

Pharmacokinetics of spinosad and milbemycin oxime administered in combination and separately per os to dogs

Holmstrom, S. D., Totten, M. L., Newhall, K. B., Qiao, M., Riggs, K. L. Pharmacokinetics of spinosad and milbemycin oxime administered in combination and separately per os to dogs. J. vet. Pharmacol. Therap  35 , 351–364. Pharmacokinetic (PK) studies were conducted to determine the potential PK interactions when spinosad and milbemycin oxime (MBO) are administered simultaneously. Investigations used commercial MBO tablets (C‐MBO; Interceptor^® Flavor Tabs, active ingredient MBO, Novartis Animal Health, Greensboro, NC, USA), novel‐source (Elanco) MBO (E‐MBO) in a gelatin capsule, spinosad API (Active Pharmaceutical Ingredient using registered manufacturing process) in a gelatin capsule, spinosad tablets (Comfortis^® chewable beef flavored tablets, active ingredient spinosad, Elanco Animal Health, Greenfield, IN, USA), and the recently registered spinosad + E‐MBO combination tablets (Trifexis? chewable beef flavored tablets, active ingredients E‐MBO and spinosad, Elanco Animal Health, Greenfield, IN, USA). Regardless of the source of MBO, in the presence of spinosad, greater systemic exposure of MBO was obtained as compared to MBO administered alone. Target animal safety studies conducted with dose multiples of spinosad and MBO indicate the increased exposure of MBO does not have implications on adverse clinical reactions. Further research is required to determine whether the higher levels of MBO have any implications for improved effectiveness as compared to C‐MBO. Effectiveness studies conducted with 0.5 mg/kg of E‐MBO in combination tablets demonstrated noninterference against C‐MBO with both products achieving >99% effectiveness against the dose‐limiting nematode, Ancylostoma caninum. No statistical differences were detected in the PK of MBO when comparing animals receiving E‐MBO (without spinosad) and C‐MBO. Also, the PK of spinosad was unaltered when co‐administered with MBO.