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.     

Pharmacokinetics of metoclopramide in goats

The pharmacokinetics of a parenteral formulation of metoclopramide (monochloride monohydrate) were determined following single intravenous (i.v.) and intramuscular (i.m.) 0.5-mg/kg doses to two groups of 4 goats in a crossover design. Mean serum concentrations of metoclopramide following i.v. administration of 0.5 mg/kg declined rapidly from a peak of 277.5 ng/ml at 3 min post-dosing to 25 ng/ml at 90 min. Serum concentrations were not detectable by 120 min after drug administration. The curve of serum concentrations vs. time was characteristic of a two-compartment open model. Mean parameters from analysis of the individual i.v. data gave a biological half-life of 0.62 h and a volume of distribution of the central compartment of 1.34 l/kg. Serum concentrations of metoclopramide following i.m. administration of 0.5 mg/kg rose rapidly to a peak of 160.9 ng/ml at 15 min post-dosing and then declined in parallel with the elimination phase of the i.v. study. These data were best described by a two-compartment open model with first-order absorption. The mean biological half-life was 1.04 h. There were no adverse reactions associated with metoclopramide at the 0.5-mg/kg dose administered by either route.     

Pharmacokinetics of difloxacin in goats

The pharmacokinetic properties of difloxacin following intravenous (i.v.) and intramuscular (i.m.) administration in goats were investigated. Difloxacin was administered in a single dose of 5 mg/kg body weight for both routes and was assayed in biological fluids (serum and urine) to determine its concentrations, kinetic behaviour and systemic availability. Following a single i.v. injection, the serum difloxacin level was best approximated to follow a two-compartment open model using weighted non-linear regression analysis. The elimination half-life (t1/2 beta) was 6.3 +/- 0.11 h. The volume of distribution at steady-state (Vdss) was 1.1 +/- 0.012 L/kg and the total body clearance (Cltot) was 0.13 +/- 0.001 L/kg/h. Following a single i.m. administration, difloxacin was rapidly absorbed and the mean peak serum concentration (4.1 +/- 0.23 micrograms/ml) was achieved 1 h post administration. The extent of serum protein binding of difloxacin in goats was 13.79 +/- 1.02% and the systemic availability was 95.4 +/- 1.17%. Following i.m. injection of difloxacin at a dose rate of 5 mg/kg b.wt for 5 consecutive days, the drug could not be detected in serum and urine at 4th day from the last injection.     

Diazepam and chlorpromazine stimulate feeding in dwarf goats

5 adult dwarf goats were injected intravenously with diazepam, chlorpromazine or isotonic saline. Both diazepam at 0.04 mg/kg and chlorpromazine at 0.5 mg/kg significantly stimulated food intake above the control 0.9% NaCl levels. The stimulatory effect appears to be most pronounced within the first 15 min post injection, and was no longer evident between 30 and 45 min after the bolus injection of the tranquillizers.     

Diazepam and chlorpromazine stimulate feeding in dwarf goats

5 adult dwarf goats were injected intravenously with diazepam, chlorpromazine or isotonic saline. Both diazepam at 0.04 mg/kg and chlorpromazine at 0.5 mg/kg significantly stimulated food intake above the control 0.9% NaCl levels. The stimulatory effect appears to be most pronounced within the first 15 min post injection, and was no longer evident between 30 and 45 min after the bolus injection of the tranquillizers.     

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.     

Pharmacokinetics of nine sulphonamides in goats

Pharmacokinetics of nine sulphonamides was investigated in healthy goats. From the plasma disappearance curves after intravenous bolus injection clearance rates, plasma half-lives and distribution volumes were calculated. Plasma-protein binding was measured in vitro and in vivo. The highest-bound sulphonamides showed the highest concentration dependence of protein binding.
Plasma disappearance curves were in accordance with the one-, two- or three-compartment pharmacokinetic models. Disposition of sulphadimidine after 100 or 200 mg/kg and of sulphisomidine after 200 mg/kg showed limited enzyme capacity characteristics. Disposition of sulphadimidine, sulphisomidine and sulphadimethoxine was dose-dependent. Goats could also be divided in fast and slow sulphadimidine eliminators. Correlation was found only between clearance and half-life. Dosage regimens were calculated for seven sulphonamides.     

Spectrofluorometric assay of chlorpromazine, half-life and pharmacokinetics of chlorpromazine in goats of different ages.

The pharmacokinetics studies in 48 experiments on the animals of different ages showed that the half-life of CPZ in kids (new born, 1 week and 3 weeks old) and goats (3 months old and adult animals) ranged from 1.47 to 1.86 hour while distribution half-life was only 0.11 to 0.17 hour. Volume of distribution of CPZ in kids and goats was much higher than 1 which indicated that the drug was extensively localized in the tissues. The elimination of CPZ was more rapid in the adult goats than in the kids. The half-life of CPZ was short and elimination was rapid in the goats as compared to the literature values for man, rat and dog. The differences are attributed primarily to the more rapid metabolism of CPZ in the goats than in the kids or man, rat and dog.     

Pharmacokinetics of imidocarb in normal dogs and goats

The pharmacokinetics of imidocarb were studied in seven mongrel dogs and eight crossbred goats. An intravenous bolus dose (4 mg/kg) of 12% imidocarb dipropionate solution wasinjected into the cephalic vein in dogs and the jugular vein in goats. The plasma concentration of imidocarb was measured by spectro-photometry. The experimental data were analysed using a two-compartment open model. The apparent volume of the central compartment was significantly higher ( P <0.01) in dogs than in goats. The significantly larger ( P <0.05) apparent specific volume of distribution in goats than in dogs may be attributed to passive diffusion followed by ion trapping of the drug in rumen fluid. Neither the half-life nor body clearance differed significantly between dogs ( t _1/2, 207 ± 45 min; Cl_B , 1.47 ± 0.38 ml/min kg) and goats ( t _1/2, 251 ± 94 min; Cl_B , 1.62 ± 0.50 ml/min kg). While almost 80% of the dose had been eliminated at 8 h in. both species, the high ratio of the imidocarb level in the peripheral-to-central compartment in goats suggests that a prolonged period may be required for complete elimination of the drug.     

Pharmacokinetics of moxidectin and doramectin in goats.

The pharmacokinetic behaviour of doramectin after a single subcutaneous administration and moxidectin following a single subcutaneous or oral drench were studied in goats at a dosage of 0.2 mg kg(-1). The drug plasma concentration-time data were analysed by compartmental pharmacokinetics and non-compartmental methods. Maximum plasma concentrations of moxidectin were attained earlier and to a greater extent than doramectin (shorter t(max) and greater C(max) and AUC than doramectin). MRT of doramectin (4.91 +/- 0.07 days) was also significantly shorter than that of moxidectin (12.43 +/- 1.28 days). Then, the exposure of animals to doramectin in comparison with moxidectin was significantly shorter. The apparent absorption rate of moxidectin was not significantly different after oral and subcutaneous administration but the extent of absorption, reflected in the peak concentration (C(max)) and the area under the concentration-time curve (AUC), of the subcutaneous injection (24.27 +/- 1.99 ng ml(-1) and 136.72 +/- 7.35 ng d ml(-1) respectively) was significantly greater than that of the oral administration (15.53 +/- 1.27 ng ml(-1) and 36.72 +/- 4.05 ng d ml(-1) respectively). The mean residence time (MRT) of moxidectin didn't differ significantly when administered orally or subcutaneously. Therefore low oral bioavailability and the early emergence of resistance in this minor species may be related. These results deserve to be correlated with efficacy studies for refining dosage requirements of endectocides in this species.     

Pharmacokinetics and dosage of aspirin in cattle.

Sodium salicylate was given intravenously to clinically normal cows, and aspirin (acetylsalicylic acid) was given orally to arthritic and clinically normal cattle. Despite slow absorption (half-time of absorption, 2.91 hours) of orally administered aspirin and rapid elimination (biologic half-life, 32 minutes) of salicylates, oral dosage of 100 mg/kg every 12 hours maintained serum salicylate concentration greater than 30 mug/ml, which was considered to be therapeutically effective.     

Pharmacokinetics and intramuscular bioavailability of cefuroxime sodium in goats

The pharmacokinetics of cefuroxime sodium, 20 and 40 mg kg(-1), were studied after i.v. and intramuscular injections in goats. Following single i.v. injections the serum concentration time curves of cefuroxime sodium were best fitted to a two-compartment open model. The drug was rapidly distributed with half-lives of distribution (t(1/2 alpha)) of 0.250 hours and 0.266 hours, and rapidly eliminated with half-lives of elimination (t(1/2 beta)) of 1.482 hours and 1.416 hours, respectively, following single i.v. injections of 20 and 40 mg kg(-1)body weight. After single intramuscular injections of cefuroxime sodium at the same doses, the mean absorption time (MAT) values were 1.379 and 1.716 hours and the peak serum concentration, C(max), was 12.965 and 38.50 microg ml(-1), attained after 0.515 and 0.608 hours (t(max)), respectively. The elimination half-lives (t(1/2el)) were 2.088 and 2.114 hours and the mean residence times (MRT) were 3.198 and 3.237 hours for 20 and 40 mg kg(-1)body weight, respectively. After both i.v. and intramuscular injections of cefuroxime sodium, the concentrations of cefuroxime in urine were much higher than that in serum. Urinary drug concentrations decreased gradually to reach their lowest levels at 24 and 48 hours post-injection, respectively. The systemic bioavailability of cefuroxime sodium in goats after intramuscular injections of 20 and 40 mg kg(-1)body weight was 88.4 per cent and 103.5 per cent, respectively. In vitro protein binding of cefuroxime sodium in goat's serum was low, ranging from 13.3 per cent to 21.6 per cent with an average of 17.0 per cent.     

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.     

Pharmacokinetics and bioavailability of chloramphenicol in normal and febrile goats

The effect of induced fever on the plasma concentrations and disposition kinetics of chloramphenicol (CHPC) was studied in adult goats. Fever was induced and maintained for 12 h by injecting Escherichia coli endotoxin (0.1 microgram/kg, i.v.) and repeating it at half the dose (0.05 microgram/kg) 8 h later. Pharmacokinetics of CHPC was studied in both normal (n = 6) and febrile (n = 6) animals following intravenous administration of CHPC Na-succinate (25 mg/kg). Intramuscular bioavailability of the drug was also investigated in both normal and febrile animals. Pharmacokinetics of CHPC following intravenous administration could be described by a two-compartment open model in both normal and febrile animals. In normal animals the half-life of CHPC was 73.0 +/- 4.95 min and the volume of distribution was 2.217 +/- 0.24 l/kg. These and other pharmacokinetic parameters did not differ significantly (P less than 0.05) between normal and febrile animals, except for Cop and A. Absorption of CHPC following intramuscular administration was good as indicated by its high bioavailability in both normal (83.34%) and febrile (81.98%) animals. Volume of distribution is usually expected to change when the febrile state is induced. Lack of such an effect in the present study could be due to high individual variation, or to the fact that CHPC already has a relatively large volume of distribution, which is less likely to be altered by a febrile state of short duration.     

Pharmacokinetics of danofloxacin 18% in lactating sheep and goats

The pharmacokinetics of danofloxacin administered at 6 mg/kg bodyweight by the intravenous and subcutaneous (s.c.) routes were determined in sheep and goats. Milk concentrations were also determined following s.c. administration. Plasma and milk concentrations of danofloxacin were measured using high-performance liquid chromatography. The plasma concentration-time curves were analysed by noncompartmental methods. Danofloxacin had a similar large volume of distribution at steady state in sheep and goats of 2.19 +/- 0.28 and 2.43 +/- 0.13 L/kg, and a similar body clearance of 0.79 +/- 0.15 and 0.98 +/- 0.13 L/kg.h, respectively. Following s.c. administration, danofloxacin achieved a similar maximum concentration in sheep and goats of 1.48 +/- 1.54 and 1.05 +/- 0.09 mg/L, respectively at 1.6 h and had a mean residence time of 4.93 +/- 0.79 and 4.51 +/- 0.44 h, respectively. Danofloxacin had an absolute bioavailability of 93.6 +/- 13.7% in sheep and 97.0 +/- 15.7% in goats and a mean absorption time of 2.07 +/- 0.75 and 2.01 +/- 0.53 h, respectively. Mean danofloxacin concentrations in milk after s.c. administration to sheep were approximately 10 times higher than plasma at 12 h postdose and remained eight times higher at 24 h postdose. In goats, mean concentration of danofloxacin in milk were approximately 13 times higher than plasma at 12 h postdose and remained four times higher at 24 h postdose. Thus, danofloxacin 18% administered s.c. to lactating ewes and goats at a dose rate of 6 mg/kg was characterized by extensive absorption, high systemic availability and high distribution into the udder resulting in higher drug concentrations being achieved in milk than in plasma.     

Pharmacokinetics and efficacy of triclabendazole in goats with induced fascioliasis

The pharmacokinetics of triclabendazole were evaluated in normal goats and in goats artificially infected with Fasciola hepatica. Triclabendazole and its metabolites were determined using a novel high performance liquid chromatographic method with fluorimetric detection after solid-phase extraction. In normal goats triclabendazole given orally was metabolized rapidly to its sulphoxide and sulphone derivatives. The maximum plasma concentrations for the sulphoxide and sulphone were similar ranging from 9 to 19 micrograms/ml and these were attained at an average 12.8 and 25.6 h, respectively, after administration. Both metabolites were eliminated slowly from plasma with elimination half-lives of 22.4 h for the sulphoxide and 19.4 h for the sulphone. They persisted at measurable concentrations in plasma for up to seven days. In milk, the two metabolites occurred in low concentrations and none of them was detectable (sulphoxide less than 0.04 microgram/ml, sulphone less than 0.02 microgram/ml) after seven days. The pharmacokinetic behaviour of triclabendazole was not altered in animals with fascioliasis. Efficacy of the drug against immature (six-week) F. hepatica was 100%.     

Pharmacokinetics of tulathromycin following subcutaneous administration in meat goats

Tulathromycin is a triamilide antibiotic that maintains therapeutic concentrations for an extended period of time. The drug is approved for the treatment of respiratory disease in cattle and swine and is occasionally used in goats. To investigate the pharmacokinetics of tulathromycin in meat goats, 10 healthy Boer goats were administered a single 2.5 mg/kg subcutaneous dose of tulathromycin. Plasma concentrations were measured by ultra-high pressure liquid chromatography tandem mass spectrometry (UPLC–MS/MS) detection. Plasma maximal drug concentration (C_max) was 633 ± 300 ng/ml (0.40 ± 0.26 h post-subcutaneous injection). The half-life of tulathromycin in goats was 110 ± 19.9 h. Tulathromycin was rapidly absorbed and distributed widely after subcutaneous injection 33 ± 6 L/kg. The mean AUC of the group was 12,500 ± 2020 h ng/mL for plasma. In this study, it was determined that the pharmacokinetics of tulathromycin after a single 2.5 mg/kg SC injection in goats were very similar to what has been previously reported in cattle.