Metabolic profile and ruminal and abomasal pH in sheep subjected to intravenous ranitidine / Perfil metabólico ruminal e pH abomasal em ovinos tratados com ranitidina por via intravenosa

Brazilian sheep production has intensified, predisposing sheep to an increased incidence of digestive disorders, such as abomasal ulcers. Ranitidine is used to prevent and treat this disease; however, there is little information on the parenteral use of this drug in adult ruminants. Few data exist on the concomitant metabolic changes and the behavior of the digestive system associated with its use. For this study, five healthy male sheep with ruminal and abomasal cannulas were used. A 5x5 Latin square experiment with a 2x2+1 factorial arrangement of the treatments was performed. Sheep treated with drug doses of 1 or 2mg/kg ranitidine administered intravenously every 8 or 12 hours were compared with the control group, was treated intravenously with 1 mL of physiological solution per 25 kg every 12 hours. Higher total protein concentrations, hemoglobin levels, as well as increased aspartate aminotransferase activity and increased abomasal pH for up to 150 min following drug administration were observed in all animals that received the drug, regardless of dose and frequency. The animals treated every 12 hours showed a decrease in leukocyte number compared with the control group and with the animals treated every 8 hours. Increased serum creatinine concentrations were observed in the animals treated every 8 hours. Treatments of 1mg/kg every 8 hours and 2mg/kg every 12 hours increased the red blood cell count and decreased the serum pepsinogen. All protocols studied were safe for healthy sheep, but 1mg/kg ranitidine every 8 hours and 2mg/kg ranitidine every 12 hours were the most effective protocols for gastric protection.(AU)

A ovinocultura brasileira tem se intensificado, o que predispõe os animais à maior incidência de transtornos digestivos, como a úlcera de abomaso. A ranitidina é utilizada na prevenção e tratamento desta afecção, no entanto há pouca informação sobre a indicação parenteral deste fármaco para ruminantes adultos. São escassas as informações a respeito das alterações metabólicas e do comportamento do sistema digestório associados ao seu uso. Para este estudo foram utilizados cinco ovinos, machos, hígidos, providos de cânula ruminal e abomasal. O delineamento foi Quadrado Latino 5x5 com arranjo fatorial de tratamentos 2x2+1. Os ovinos tratados com as doses de 1 e 2mg/kg de ranitidina administrada por via intravenosa a cada 8 ou 12 horas foram comparados aos animais do grupo controle, tratados por via intravenosa com 1mL de solução fisiológica por 25 kg a cada 12 horas. Maiores concentrações de proteína total e hemoglobina, maiores atividades de AST e aumento do pH abomasal por até 150 minutos foram observados em todos os animais que receberam o fármaco, independentemente de dose e frequência. Os animais tratados a cada 12 horas mostraram diminuição do número de leucócitos comparados aos animais tratados a cada 8 horas e aos animais do grupo controle. Observou-se aumento das concentrações de creatinina nos animais tratados a cada 8 horas. Os tratamentos 1mg/kg a cada 8 horas e 2mg/kg a cada 12 horas aumentaram o número de hemácias e diminuíram as concentrações séricas de pepsinogênio. Todos os protocolos estudados foram seguros para ovinos sadios, porém 1mg/kg de ranitidina a cada 8 horas e 2mg/kg a cada 12 horas mostraram-se mais eficientes quanto à proteção gástrica.

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

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

Contrast-enhanced ultrasound analysis of renal perfusion in normal micropigs

Contrast-enhanced ultrasound is one of method for evaluating renal perfusion. The purpose of this project was to assess perfusion patterns and dynamics in normal micropig kidney using ultrasonographic contrast media. Eight young healthy micropigs were included in this study. Micropigs were anesthetized with propofol and received an intravenous bolus of microbubble contrast media through an ear vein. Time/mean pixel value (MPV) curves were generated for selected regions in the right renal cortex and medulla. The parenchyma was enhanced in two phases. The cortex was first enhanced followed by a more gradual enhancement of the medulla. A significant difference in perfusion was detected between the cortex and medulla. Following the bolus injection, the average upslope was 0.68 +/- 0.27 MPV/sec, downslope was -0.27 +/- 0.13 MPV/sec, baseline was 73.9 +/- 16.5 MPV, peak was 84.6 +/- 17.2 MPV, and time-to-peak (from injection) was 17.5 +/- 6.6 sec for the cortex. For the medulla, the average upslope was 0.50 +/- 0.24 MPV/sec, downslope was -0.12 +/- 0.06 MPV/sec, baseline was 52.7 +/- 7.0 MPV, peak was 65.2 +/- 9.3 MPV, and time-to-peak (from injection) was 27.5 +/- 5.0 sec. These data can be used as normal reference values for studying young micropigs.

Disposition kinetics and urinary excretion of cefpirome after intravenous injection in buffalo calves

We investigated the disposition kinetics and urinary excretion of cefpirome in buffalo calves after a single intravenous administration of 10 mg/kg. Also, an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of cefpirome in the plasma was 57.4 +/- 0.72 microgram/ml, which declined to 0.22 +/- 0.01 microgram/ml at 24 h. The cefpirome was rapidly distributed from the blood to the tissue compartment as shown by the high distribution coefficient values (8.67 +/- 0.46/h), and by the drug's rate of transfer constant from the central to the peripheral compartment, K12 (4.94 +/- 0.31/h). The elimination halflife and the volume of distribution were 2.14 +/- 0.02 h and 0.42 +/- 0.005 l/kg, respectively. Once the distribution equilibrium was reached between the tissues and plasma, the total body clearance (ClB) and the ratio of the drug present in the peripheral to the central compartment (T/P ratio) were 0.14 +/- 0.002 l/kg/h and 1.73 +/- 0.06, respectively. Based on the pharmacokinetic parameters we obtained, an appropriate intravenous cefpirome dosage regimen for treating cefpiromesensitive bacteria in buffalo calves would be 8.0 mg/kg repeated at 12 h intervals for 5 days, or until persistence of the bacterial infection occurred.

Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and oral administration in pigs

The pharmacokinetics and dosage regimen of norfloxacin-glycine acetate (NFLXGA) was investigated in pigs after a single intravenous (i.v.) or oral (p.o.) administration at a dosage of 7.2 mg/kg body weight. After both i.v. and p.o. administration, plasma drug concentrations were best fitted to an open two-compartment model with a rapid distribution phase. After i.v. administration of NFLXGA, the distribution (t1/2alpha) and elimination half-life (t1/2beta) were 0.36 +/- 0.07 h and 7.42 +/- 3.55 h, respectively. The volume of distribution of NFLXGA at steady state (Vdss) was 4.66 +/- 1.39 l/kg. After p.o. administration of NFLXGA, the maximal absorption concentration (Cmax) was 0.43 +/- 0.06 microgram/ ml at 1.36 +/- 0.39 h (Tmax). The mean absorption (t1/2ka) and elimination half-life (t1/2beta) of NFLXGA were 0.78 +/- 0.27 h and 7.13 +/- 1.41 h, respectively. The mean systemic bioavailability (F) after p.o. administration was 31.10 +/- 15.16%. We suggest that the optimal dosage calculated from the pharmacokinetic parameters is 5.01 mg/kg per day i.v. or 16.12 mg/kg per day p.o.

Disposition kinetics and dosage regimen of levofloxacin on concomitant administration with paracetamol in crossbred calves

The disposition kinetics of levofloxacin was investigated in six male crossbred calves following single intravenous administration, at a dose of 4 mg/kg body weight, into the jugular vein subsequent to a single intramuscular injection of paracetamol (50 mg/kg). At 1 min after the injection of levofloxacin, the concentration of levofloxacin in plasma was 17.2 +/- 0.36 microgram/ml, which rapidly declined to 6.39 +/- 0.16 microgram/ml at 10 min. The drug level above the MIC90 in plasma, was detected for up to 10 h. Levofloxacin was rapidly distributed from blood to the tissue compartment as evidenced by the high values of the distribution coefficient, alpha (17.3 +/- 1.65 /h) and the ratio of K12/K21 (1.83 +/- 0.12). The values of AUC and Vdarea were 12.7 +/- 0.12 microgram.h/ml and 0.63 +/- 0.01 l/kg. The high ratio of the AUC/MIC (126.9 +/- 1.18) obtained in this study indicated the excellent antibacterial activity of levofloxacin in calves. The elimination half-life, MRT and total body clearance were 1.38 +/- 0.01 h, 1.88 +/- 0.01 h and 0.32 +/- 0.003 l/kg/h, respectively. Based on the pharmacokinetic parameters, an appropriate intravenous dosage regimen for levofloxacin would be 5 mg/kg repeated at 24 h intervals when prescribed with paracetamol in calves.

Pharmacokinetics and bioavailability of doxycycline in ostriches (Struthio camelus) at two different dose rates

A bioavailability and pharmacokinetics study of doxycycline was carried out on 30 healthy ostriches after a single intravenous (IV), intramuscular (IM) and oral dose of 15 mg/kg body weight. The plasma doxycycline concentration was determined by HPLC/UV at 0 (pretreatment), 0.08, 0.25, 0.5 1, 2, 4, 6, 8, 12, 24 and 48 h after administration. The plasma concentration-time curves were examined using non-compartmental methods based on the statistical moment theory for only the higher dose. After IV administration, the elimination half-life (t(1/2beta)), mean residence time (MRT), volume of distribution at the steady-state (V(ss)), volume of distribution (Vd(area)) and total body clearance (Cl(B)) were 7.67 +/- 0.62 h, 6.68 +/- 0.86 h, 0.86 +/- 0.16 l/kg, 1.67 +/- 0.52 l/kg and 2.51 +/- 0.63 ml/min/kg, respectively. After IM and oral dosing, the mean peak plasma concentrations (C(max)) were 1.34 +/- 0.33 and 0.30 +/- 0.04 microgram/ml, respectively, which were achieved at a postadministration time (t(max)) of 0.75 +/- 0.18, 3.03 +/- 0.48 h, respectively. The t(1/2beta), Vd(area) and Cl(B) after IM administration were 25.02 +/- 3.98 h, 23.99 +/- 3.4 l/kg and 12.14 +/- 1.71 ml/min/kg, respectively and 19.25 +/- 2.53 h, 61.49 +/- 7 l/kg and 40.19 +/- 3.79 ml/min/kg after oral administration, respectively. The absolute bioavailability (F) of doxycycline was 5.03 and 17.52% after oral and IM administration, respectively. These results show that the dose data from other animals particularly mammals cannot be extrapolated to ostriches. Therefore, based on these results along with those reported in the literature, further studies on the pharmacokinetic/pharmacodynamic, in vitro minimum inhibitory concentration values and clinical applications of doxycycline in ostriches are required.