Pharmacokinetics, urinary and mammary excretion of ceftriaxone in lactating goats

The pharmacokinetic properties of ceftriaxone were investigated in 10 goats following a single intravenous (i.v.) and intramuscular (i.m.) administration of 20 mg kg(-1) body weight. After i.v. injection, ceftriaxone serum concentration-time curves were characteristic of a two-compartment open model. The distribution and elimination half-lives (t(1/2alpha), t(1/2beta)) were 0.12 and 1.44 h respectively. Following i.m. injection, peak serum concentration (C(max)) of 23.6 microg ml(-1) was attained at 0.70 h. The absorption and elimination half-lives (t(1/2ab), t(1/2el)) were 0.138 and 1.65 h respectively. The systemic bioavailability of the i.m. administration (F %) was 85%. Following i.v. and i.m. administration, the drug was excreted in high concentrations in urine for 24 h post-administration. The drug was detected at low concentrations in milk of lactating goats. A recommended dosage of 20 mg kg(-1) injected i.m. every 12 h could be expected to provide a therapeutic serum concentration exceeding the minimal inhibitory concentrations for different susceptible pathogens.     

Pharmacokinetics and urinary excretion of sulphadimidine in sheep and goats

Pharmacokinetics and urinary excretion of sulphadimidine were determined in sheep and goats following a single intravenous injection (100 mg/kg). The disposition of the drug was described in terms of exponential expression: C _p= Be ^-βt. Based on total (free and bound) sulphonamide level in plasma, pseudo-distribution equilibrium was rapidly attained and the half-life for elimination was 3.88 ± 0.64 h and 4.00 ± 0.34 h in sheep and goats, respectively. Body clearance, which is the sum of all clearance processes was 88 ± 19 and 55 ± 4 ml/kg/h in sheep and goats. Based on this study a satisfactory intravenous dosage regimen might consist of 100 and 60 mg sulphadimidine/kg body wt for sheep and goats and should be repeated at 12 h intervals. The influence of disease conditions on predicted plasma levels remain to be verified experimentally. Three-quarters of an intravenously injected dose of sulphadimidine was excreted in the urine of sheep and goats within 24 h of administration. The drug was mainly excreted as free amine while acetylated drug constituted 7 and 8% of total drug content in the urine of sheep and goats, respectively.     

Absorption, metabolism and excretion of 3-acetyl DON in pigs.

The absorption, metabolism and excretion of 3-acetyldeoxynivalenol (3-aDON) in pigs were studied. Pigs with a faecal microflora known to be able to de-epoxidate trichothecenes were used in the experiment. The pigs were fed a commercial diet with 3-aDON added in a concentration of 2.5 mg/kg feed for 2.5 days. No traces of 3-aDON or its de-epoxide metabolite were found in plasma, urine or faeces. Deoxynivalenol (DON) was detected in plasma as soon as 20 min after start of the feeding. The maximum concentration of DON in plasma was reached after 3 h and decreased rapidly thereafter. Only low concentrations close to the detection limit were found in plasma 8 h after start of the feeding. A significant part of the DON in plasma was in a glucuronide-conjugated form (42 +/- 7%). No accumulation of DON occurred in plasma during the 60 h of exposure. The excretion of DON was mainly in urine (45 +/- 26% of the toxin ingested by the pigs) and only low amounts of metabolites of 3-aDON (2 +/- 0.4%) were recovered in faeces. De-epoxide DON constituted 52 +/- 15% of the total amount of 3-aDON-metabolites detected in faeces. The remaining part in faeces was DON. DON was still present in the urine and faeces at the end of the sampling period 48 h after the last exposure. The results show that no de-epoxides are found in plasma or urine in pigs after trichothecene exposure, even in pigs having a faecal microflora with a de-epoxidation activity. The acetylated form of the toxin is deacetylated in vivo. Furthermore, the experiment shows that the main part of DON is rapidly excreted and does not accumulate in plasma, but a minor part of the toxin is retained and slowly excreted from the pigs.     

The pharmacokinetics, metabolism and urinary detection time of tramadol in camels

The pharmacokinetics of tramadol in camels (Camelus dromedarius) were studied following a single intravenous (IV) and a single intramuscular (IM) dose of 2.33 mg kg(-1) bodyweight. The drug's metabolism and urinary detection time were also investigated. Following both IV and IM administration, tramadol was extracted from plasma using an automated solid phase extraction method and the concentration measured by gas chromatography-mass spectrometry (GC/MS). The plasma drug concentrations after IV administration were best fitted by an open two-compartment model. However a three-compartment open model best fitted the IM data. The results (means+/-SEM) were as follows: after IV drug administration, the distribution half-life (t(1/2)(alpha)) was 0.22+/-0.05 h, the elimination half-life (t(1/2)(beta)) 1.33+/-0.18 h, the total body clearance (Cl(T)) 1.94+/-0.18 L h kg(-1), the volume of distribution at steady state (Vd(ss)) 2.58+/-0.44 L kg(-1), and the area under the concentration vs. time curve (AUC(0-infinity)) 1.25+/-0.13 mg h L(-1). Following IM administration, the maximal plasma tramadol concentration (C(max)) reached was 0.44+/-0.07 microg mL(-1) at time (T(max)) 0.57+/-0.11h; the absorption half-life (t(1/2 ka)) was 0.17+/-0.03 h, the (t(1/2)(beta)) was 3.24+/-0.55 h, the (AUC(0-infinity)) was 1.27+/-0.12 mg h L(-1), the (Vd(area)) was 8.94+/-1.41 L kg(-1), and the mean systemic bioavailability (F) was 101.62%. Three main tramadol metabolites were detected in urine. These were O-desmethyltramadol, N,O-desmethyltramadol and/or N-bis-desmethyltramadol, and hydroxy-tramadol. O-Desmethyltramadol was found to be the main metabolite. The urinary detection times for tramadol and O-desmethyltramadol were 24 and 48 h, respectively. The pharmacokinetics of tramadol in camels was characterised by a fast clearance, large volume of distribution and brief half-life, which resulted in a short detection time. O-Desmethyltramadol detection in positive cases would increase the reliability of reporting tramadol abuse.     

The pharmacokinetics, metabolism and urinary detection time of caffeine in camels

The pharmacokinetics of caffeine were determined in 10 camels after an intravenous dose of 2.35 mg kg(-1). The data obtained (median and range) were as follows. The elimination half-life (t(1/2)) was 31.4 (21.2 to 58.9) hours, the steady state volume of distribution (V(SS)) was 0.62 (0.51 to 0.74) litre kg(-1)and the total body clearance (Cl(T)) was 14.7 (8.70 to 19.7) ml kg(-1)per hour. Renal clearance estimated in two camels was 0.62 and 0.34 ml kg(-1)per hour. In vitro plasma protein binding (mean +/-SEM, n = 10) to a concentration of 2 and 8 microg ml(-1)was 36.0 +/- 0.24 and 39.2 +/- 0.36 per cent respectively. Theophylline and theobromine were identified as caffeine metabolites in serum and urine. The terminal elimination half-life of the former, estimated in two camels, was 70. 4 and 124.4 hours. Caffeine could be detected in the urine for 14 days.     

The effect of age on phenylbutazone pharmacokinetics, metabolism and plasma protein binding in goats

Phenylbutazone (PBZ) was administered intravenously as a single dose (10 mg/ kg) to adult male and 1-day-, 10-day-, 4-week- and 6 week-old male goats. The plasma concentration of PBZ and its major metabolites oxyphenbutazone (OPBZ) and γ-hydroxyphenbutazone (γ-OHPBZ) was measured over time. The elimination half-life (t_½β) of PBZ decreased from 120 h in the 1-day-old to 16 h in the adult goats. Although the volume of distribution ( V _d) did not change significantly during maturation, the total body clearance ( Cl B) increased from 2 ml.h^-1.kg^-1 in I-day-old t o 13 ml.h^-1.kg^-1 in the adult goats; the increase was 2-fold in the first 10 days of life. Oxyphenbutazone was detectable in the plasma of adult and 6-week-old goats as early as 15 min after PBZ administration. Its peak concentration occurred at 1.5 h (1.6 μg/ml) in adults and at 6 h (0.95 μg/ml) and 12 h (0.36 μg/ml) in 6- and 4-week-old goats respectively. The highest plasma concentration of γ-OHPBZ was achieved in 4-week-old followed by 6-week-old and adult animals.     

Disposition kinetics and urinary excretion of ciprofloxacin in goats following single intravenous administration

We evaluated the pharmacokinetics of ciprofloxacin in serum (n = 6) and urine (n = 4) in goats following a single intravenous administration of 4 mg/kg body weight. The serum concentration-time curves of ciprofloxacin were best fitted by a two-compartment open model. The drug was detected in goat serum up to 12 h. The elimination rate constant (β) and elimination half-life (t_1/2β) were 0.446 ± 0.04 h^-1 and 1.630 ± 0.17 h, respectively. The apparent volume of distribution at steady state (Vd_ss) was 2.012 ± 0.37 l/kg and the total body clearance (Cl_B) was 16.27 ± 1.87 ml/min/kg. Urinary recovery of ciprofloxacin was 29.70% ± 10.34% of the administered dose within 36 h post administration. In vitro serum protein binding was 41% ± 13.10%. Thus, a single daily intravenous dose of 4 mg/kg is sufficient to maintain effective levels in serum and for 36 h in urine, allowing treatment of systemic, Gram-negative bacterial infections and urinary tract infections by most pathogens.     

Isometamidium in goats: disposition kinetics, mammary excretion and tissue residues

The pharmacokinetics of the antitrypanosomal drug isometamidium were studied in lactating goats after intravenous and intramuscular administration at a dose of 0.5 mg/kg body weight, in a crossover design at an interval of 6 weeks. Following intravenous administration, the half-life of the disappearance of the drug from plasma during the terminal phase was 3.2 h, and the mean residence time was 2.4 h. The apparent volume of distribution averaged 1.52 l/kg, and the mean total body clearance was 0.308 l/kg/h. After intramuscular administration, the absolute bioavailability was low, averaging 27%. This was consistent with a low mean maximum concentration of 24 ng/ml which occurred after 6 h. No drug was detectable (less than 10 ng/ml) in milk samples collected over a period of 14 days following drug administration by either the intravenous or intramuscular route. In tissues analysed when the goats were killed 6 weeks after administration of the second dose, no drug was detectable (less than 0.4 micrograms/g wet tissue) in the liver, kidney and muscle. However, at the injection site, drug concentrations varied from less than 0.4 to 18.8 micrograms/g wet tissue.     

Metocurine pharmacokinetics and pharmacodynamics in goats

Non-depolarizing muscle relaxants can facilitate surgery and anaesthesia in numerous species, and volatile inhalational anaesthetics such as isoflurane potentiate their action. We studied the effect of isoflurane on the pharmacodynamics and pharmacokinetics of metocurine in six goats. Each was studied twice: once during barbiturate-opiate anaesthesia and once during isoflurane anaesthesia. The evoked response to sciatic nerve stimulation was measured using a force transducer attached to the hoof. Metocurine was infused until approximately 80–90% blockade. Plasma metocurine concentration was determined by high-performance liquid chromatography. Isoflurane increased the potency of metocurine significantly; IC₅₀ (the concentration in the effect compartment at 50% paralysis) was 70 ± 15 ng/mL during isoflurane anaesthesia and 129 ± 42 ng/mL during barbiturate-opiate anaesthesia ( P < 0.03). Volume of distribution (63 ± 18 mL/kg), clearance (1.6 ± 0.4 mL/min±kg) and elimination half-life (99 ± 9 min) during barbiturate-opiate anaesthesia were not significantly different during isoflurane anaesthesia: 64 ± 25 mL/kg, 1.5 ± 0.7 mL/kgmin, 116 ± 16 min respectively. We conclude that, relative to barbiturate-opiate anaesthesia, isoflurane potentiates metocurine in goats.     

The effect of testosterone and rutting on the metabolism and pharmacokinetics of sulphadimidine in goats

After testosterone pretreatment of castrated goats and during the rutting season of adult entire male goats, the oxidative metabolism of sulphadimidine (SDM) was inhibited markedly compared with the castrated control state of these animals. The oxidation of the 5 position (yielding 5-hydroxysulphadimidine) and of the 6-hydroxymethyl group (yielding 6-carboxysulphadimidine) was decreased equally, with that of the methyl group at the pyrimidine side chain itself being 6-hydroxymethylsulphadimidine (CH2OH), whereas the acetylation pathway was unaffected by testosterone. The consequence of altered metabolism by testosterone was a prolongation of SDM presence in the body. Effects on protein binding of the CH2OH metabolite and on the renal clearance of SDM were also investigated.     

The pharmacokinetics, metabolism and urinary detection time of etamiphylline in camels after intramuscular administration

The pharmacokinetics of etamiphylline were determined after an intramuscular (i.m.) dose of 3.5 mg/kg body weight in six healthy camels. Furthermore, the metabolites and drug detection time were evaluated. The data obtained median and (range) were as follows: the terminal elimination half-life (t(1/2 beta), h) was 3.04 (2.03-3.62); apparent total body clearance (Cl/F, L/h/kg) was 1.27 (0.74-2.99); the apparent volume of distribution at steady state (V(ss)/F, L/kg) was 4.94 (3.57-12.54); and renal clearance (Cl(r), L/h/kg) determined in two camels was 0.005 and 0.004, respectively. The detection time of etamiphylline in urine after an i.m. dose of 3.5 mg/kg body weight ranged between 12 and 13 days. Three etamiphylline metabolites were tentatively identified in camels urine: The first one desethyletamiphylline was the main metabolite and resulted from N-deethylation of etamiphylline had a molecular weight of 251, and was detected in urine for about 13-14 days. Theophylline (molecular weight 180) was the second metabolite and resulted from ring N-dealkylation of etamiphylline. It was present in small amounts and was detected for about 5 h after drug administration in urine. The third metabolite, possibly resulted from demethylation of etamiphylline, had a molecular weight of m/z 265, and was present in small amounts and was detected in urine for about 5 h after drug administration.     

Using blood urea nitrogen to predict nitrogen excretion and efficiency of nitrogen utilization in cattle, sheep, goats, horses, pigs, and rats

The objectives of this study were to evaluate the potential for using blood urea N concentration to predict urinary N excretion rate, and to develop a mathematical model to estimate important variables of N utilization for several different species of farm animals and for rats. Treatment means (n = 251) from 41 research publications were used to develop mathematical relationships. There was a strong linear relationship between blood urea N concentration (mg/100 mL) and rate of N excretion (g x d(-1) x kg BW(-1)) for all animal species investigated. The N clearance rate of the kidney (L of blood cleared of urea x d(-1) x kg BW(-1)) was greater for pigs and rats than for herbivores (cattle, sheep, goats, horses). A model was developed to estimate parameters of N utilization. Driving variables for the model included blood urea N concentration (mg/100 mL), BW (kg), milk production rate (kg/d), and ADG (kg/d), and response variables included urinary N excretion rate (g/d), fecal N excretion rate (g/d), rate of N intake (g/d), and N utilization efficiency (N in milk and gain per unit of N intake). Prediction errors varied widely depending on the variable and species of animal, with most of the variation attributed to study differences. Blood urea N concentration (mg/100 mL) can be used to predict relative differences in urinary N excretion rate (g/d) for animals of a similar type and stage of production within a study, but is less reliable across animal types or studies. Blood urea N concentration (mg/100 mL) can be further integrated with estimates of N digestibility (g/g) and N retention (g/d) to predict fecal N (g/d), N intake (g/d), and N utilization efficiency (grams of N in milk and meat per gram of N intake). Target values of blood urea N concentration (mg/100 mL) can be backcalculated from required dietary N (g/d) and expected protein digestibility. Blood urea N can be used in various animal species to quantify N utilization and excretion rates.     

Pharmacodynamics, pharmacokinetics and faecal persistence of morantel in cattle and goats

Morantel could not be detected (<0.05 pg/ml)in the plasma of cattle or goats followingthe oral administration of morantel tartrate at a dose rate of 10 mg/kg
bodyweight. No morantel was detected in the milk of lactating goats except in
one animal where a concentration of 0.092 pg/ml was detected at 8 h after drug
administration. Morantel was highly effective against Cooperia oncophora infec-
tions in calves treated 6, 9 or 18 days after infection; however, was highly
effective against Ostertagia ostertagi only when treated 18 days after infection.
Morantel did not affect the fecundity of adult 0.ostertagi surviving treatment 18
days after infection which had similar average numbers of eggs in their uteri
(range 13.4 f 0.73-16.8 L 0.98) as did parasites from control animals (range
12.0 k 0.70-13.6 2 0.66). Morantel could be detected at a concentration of 96 k
4.5 pgig (dry weight) in the faeces of a calf 24 h after treatment with I0 mgikg
bodyweight of morantel tartrate. The concentration of morantel in replicate
samples of this faeces exposed to natural atmosphere, but not to soil or soil
organisms, declined slowly over the following 322 days. At day 322 after the start
of the experiment 8.8 pg/g of morantel could be measured in the remaining
faecal material. Throughout the faecal degradation study the concentration of
morantel in the crusts of the replicate sample pats was lower than the
concentration in the core samples.     

Mammary and renal excretion of chlorpromazine in goats

In experiments on goats it was found that the binding of chlorpromazine (Cpz) to the proteins in plasma and milk ranged between 91–99 and 91–97 %, respectively, and was independent of the drug concentration in the samples. The in vitro binding of chlorpromazine in whole milk (96%) was significantly higher (P<0.01) than the protein binding in skim milk (91%) because the drug was concentrated in the butterfat. The concentration of Cpz was always higher in the milk than in the corresponding plasma samples. The renal clearance of Cpz in goats with normal urine pH was very small (0.16 ml min^-1) due to the high degree of plasma protein binding and of back diffusion. The mechanisms involved during the renal excretion of Cpz in goats included glomerular filtration, probably active tubular secretion and pH dependent back diffusion.     

Experimental Coxiella burnetii infection in pregnant goats: excretion routes

Q fever is a widespread zoonosis caused by Coxiella burnetii. Infected animals, shedding bacteria by different routes, constitute contamination sources for humans and the environment. To study Coxiella excretion, pregnant goats were inoculated by the subcutaneous route in a site localized just in front of the shoulder at 90 days of gestation with 3 doses of bacteria (10(8), 10(6) or 10(4) i.d.). All the goats aborted whatever the dose used. Coxiella were found by PCR and immunofluorescence tests in all placentas and in several organs of at least one fetus per goat. At abortion, all the goats excreted bacteria in vaginal discharges up to 14 days and in milk samples up to 52 days. A few goats excreted Coxiella in their feces before abortion, and all goats, excreted bacteria in their feces after abortion. Antibody titers against Coxiella increased from 21 days post inoculation to the end of the experiment. For a Q fever diagnostic, detection by PCR and immunofluorescence tests of Coxiella in parturition products and vaginal secretions at abortion should be preferred to serological tests.