Pharmacokinetics of chlortetracycline in the turkey: evaluation of biliary secretion

The pharmacokinetics of chlortetracycline (CTC) in plasma and bile after intravenous administration in turkeys was ascertained. After a dose of CTC (0.9 mg/kg) was administered IV, 8.5% of the dose appeared in the bile in 4 hours. The peak bile/plasma concentration ratio for CTC was 254 at 2 hours. The bile/plasma concentration ratio was greater than 1 from 10 to 240 minutes after CTC administration.     

Pharmacokinetics and urinary excretion of sulphadimidine in buffalo calves

Pharmacokinetics and urinary excretion of sulphadimidine (SDI) were determined in buffalo calves following single oral administration (150 mg/kg). The plasma levels of free sulphadimidine were above minimum effective therapeutic concentration (> 40 micrograms/ml) between 4 and 12 h and the N4-acetylated form of the drug was in the range of 7.2-19.3%. Kinetic evaluation of plasma levels was performed using a two-compartment open model. The absorption and elimination half-lives of SDI were 3.01 and 11.94 h, respectively. Based on this study, an optimal dosage regimen of sulphadimidine in buffalo calves would be 100 mg/kg, followed by 50 mg/kg at 12 h intervals. Sulphadimidine was mainly excreted in the urine as free amine. The percentage of N4-acetyl sulphadimidine in urine was comparatively higher than in plasma.     

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, 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.     

Antibiotic aerosolization: tissue and plasma oxytetracycline concentrations in turkey poults

Oxytetracycline hydrochloride (OTC) was delivered by aerosol to healthy 3-week-old turkeys. Trachea, lung, and plasma were evaluated for OTC levels at 1, 4, 8, 12, 24, and 48 hours after aerosol exposure. In Expt. 1, 15 poults in a modified Horsfall unit were exposed to 1 g OTC/m3 of air using a DeVilbiss ultrasonic nebulizer. In Expt. 2, 25,000 poults in a commercial confinement unit were exposed to 0.075 g of OTC/m3 of air using a Fogmaster fogger. In each case, initially high tracheal and lung OTC concentrations were obtained. OTC levels in the trachea fell to less than 1 microgram/g between 4 and 8 hours postexposure. Plasma OTC levels remained low throughout both experiments. Oxytetracycline was still detectable in room air 60 min after aerosol exposure and before ventilation was restored. This method of administration may have promise for use in respiratory infections, but additional studies are needed to further define the use of aerosol therapy in poultry production units.     

Pharmacokinetics and urinary excretion of sulphadimidine in sheep during summer and winter

Pharmacokinetics and urinary excretion of sulphadimidine were investigated in sheep during summer and winter seasons. Average minimum and maximum environmental temperature in the summer ranged from 22.6 to 40.2 degrees C and in winter from 4.5 to 21.1 degrees C. The determination of plasma volume, plasma protein and packed cell volume during summer and winter revealed a significant decrease in plasma volume and a significant increase in plasma protein in the summer indicative of haemoconcentration. Packed cell volume did not differ significantly between the seasons. The pharmacokinetics of sulphadimidine were determined following a single intravenous injection (100 mg/kg) in summer and winter. Zero time plasma concentration of the drug was higher during summer than in winter. The elimination half-life of the drug was similar in summer and winter, but the apparent volume of distribution was lower in summer. Likewise, total body clearance was significantly lower in summer. Based on these studies a satisfactory intravenous dosage regimen might consist of 86 and 100 mg/kg for priming and 78 and 88 mg/kg as maintenance doses during summer and winter, respectively, the doses being repeated at 12 hour intervals. Twenty four hours after sulphadimidine administration 90 and 73 per cent of the dose was excreted in urine during summer and winter, respectively. The drug was excreted mainly as free amine.     

Pharmacokinetics of oxytetracycline hydrochloride in rabbits

Pharmacokinetics of oxytetracycline HCl (OTC) was studied in rabbits. After 10 mg of OTC/kg of body weight was administered IV, the distribution half-life was 0.06 hour, terminal half-life was 1.32 hours, volume of distribution area was 0.861 L/kg, and total body clearance was 0.434 L/kg/h. After 10 mg of OTC/kg was given IM, the absorption half-life was 2.09 hours, extent of absorption was 71.4%, and total body clearance of the absorbed fraction was 0.576 L/kg/h. Based on these kinetic data, a dosage of 15 mg of OTC/kg, every 8 hours was developed. This dose given IM for 7 consecutive days resulted in observed steady-state maximum and minimum concentrations (mean +/- SD) of 4.7 +/- 0.3 micrograms/ml and 3.2 +/- 0.6 micrograms/ml, respectively. Twice this dose (30 mg of OTC/kg, every 8 hours) given IM caused anorexia and diarrhea.     

Pharmacokinetics of penicillin G in the turkey

Parmacokinetics of penicillin G was determined for the turkey. The study was prompted by the isolation of a sulfonamide-resistant strain of Pasteurella multocida from tissues of turkeys involved in an outbreak of fowl cholera and the subsequent discovery that little pharmacologic information was available concerning other antimicrobial agents in that species. Penicillin G was chosen for study because P multocida is susceptible to this antibiotic. The elimination of the antibiotic followed first-order kinetics, and the half-life was found to be 0.5 hours. Parenteral administration of benzathine-procaine penicillin G resulted in higher concentrations, which persisted for longer periods than did procaine or potassium salts of the antibiotic.     

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.     

Biliverdin and bilirubin excretion in the turkey.

Mean endogenous bile flow in 11 turkeys was 0.81 plus or minus 0.52 mul/g of the liver per minute (10.4 plus or minus 5.3 mul/Kg of body weight per minute). Endogenous biliverdin and bilirubin excretory rates were 0.59 plus or minus 0.31 and 0.058 plus or minus 0.018 mug/g of liver per minute (7.6 plus or minus 3.6 and 0.76 plus or minus 0.23 mug/Kg of body weight per minute), respectively. Mean concentrations of biliverdin and bilirubin in endogenous bile were 92 plus or minus 55 and 8.9 plus or minus 5.2 mg/100 ml, respectively. Livers constituted 1.36 plus or minus 0.22 percent of the body weight. Thin layer chromatographic studies revealed a heterogeneity of bilirubin conjugates in bile.     

Pharmacokinetics and urinary excretion of gentamicin in Bubalus bubalis calves following intramuscular administration

The pharmacokinetics and urinary excretion of gentamicin was studied in buffalo calves after a single intramuscular administration (10 mg kg-1). Kinetic determinants were calculated by using a two compartment open model. The absorption (t1/2Ka) and biological half lives (t1/2 beta) were calculated to be 0.43 +/- 0.08 and 3.79 +/- 0.23 h, respectively. The value of the apparent volume of distribution (VdB) was found to be 0.38 +/- 0.07 litre kg-1. The satisfactory intramuscular dosage regimen of gentamicin for buffalo calves would be 3.23 mg kg-1 as priming dose and 2.88 mg kg-1 as maintenance dose to be repeated at 12 hour intervals to achieve and maintain the therapeutic plasma levels within safe limits. Urinary excretion of gentamicin was very rapid during the first 12 hours as 48.07 +/- 1.39 per cent of the total administered dose was excreted unchanged during this period.     

A novel delivery of oxytetracycline in turkey breeder hens.

A novel product (SQ12) for subcutaneous (SQ) injectable delivery of oxytetracycline (OTC) has been developed for use in livestock. SQ12 employs microfluidic spheres encasing OTC crystals, which allows for longer release of the OTC compared with other injectable antibiotics. The objectives of the study were to determine serum and tissue levels of SQ12 in turkey breeder hens to 14 days postinjection and to evaluate effects of SQ12 on reproductive status. Thirty photostimulated hens were housed in litter floor pens and provided with 14.5 hr of light per day in a curtain-sided facility. Six hens served as untreated controls. Twelve hens per treatment group received SQ injections in the neck with SQ12 at 11.4 (L dose group) or 22.7 mg/kg (H dose group) to assess low and high doses, respectively. Serum samples were obtained from each hen at predose and 6, 12, 24, 48, 72, 96, 168, 240, and 336 hr postinjection. All hens were euthanatized at 14 and 15 days postinjection. One-half of the hens in each treatment group were sampled (liver, lung, kidneys, and breast muscle) for tissue residue levels of OTC. The control group had no detectable OTC in serum or tissues at any sample collection time. There were no detectable serum levels of OTC in either treatment group prior to injection. The average serum concentrations of the L and H dose groups showed similar depletion curves although the H dose group was 42% higher at maximum concentration than the L group. Average tissue concentration of OTC for all tissues sampled from the H dose group was twice that of the L dose group. All tissue levels were below the OTC residue tolerance limit. SQ12 provided an extended source of OTC in serum of turkey breeder hens with no effect on reproductive status. SQ12 may provide for a novel treatment of bacterial infection in turkey breeder hens with longer lasting serum levels compared with other single injectable OTC products.     

Pharmacokinetics of oxytetracycline and therapeutic implications in veal calves

Pharmacokinetic parameters of oxytetracycline were analysed in healthy preruminant veal calves after intravenous, intramuscular and oral administration. The serum half-lives in the β-elimination phase of both 10% and 20% solutions after i.v. injection of 10 mg/kg were similar (7.07 ± 1.36 h and 7.16 ± 1.17 h, mean ± SD), whereas the total body clearance and the apparent volume of distribution were higher for the 20% solution. Serum concentrations above 0.5 μg/ml were maintained with both formulations during 12–24 h but were only above 4 μg/ml to 5 h. Intramuscular administration of the 20% solution gave a complete absorption with two rate constants of absorption, a faster (t_1/2a1= 0.27 h) and a slower one (t_1/2a2= 10.90 h) responsible for the delayed elimination half-life after this route of application (t_1/2β= 9.83 ± 1.35 h). Mean serum concentrations reached a maximum level of 3.01 ± 0.72 μg/ml at 4.01 ± 2.84 h and decreased to 0.5 μg/ml between 12 and 24 h. 50 mg/kg given orally with a milk replacer were found to have a mean bioavailability of 46.35%. A mean serum peak level of 4.99 ± 1.37 μg/ml was achieved at 9.16 ± 1.99 h and the mean concentration was still above 0.5 μg/ml after 48 h. The elimination half-life (t_1/2β= 10.66 ± 3.15 h) reflected the slow absorption step (t_1/2a2= 10.15 h) following that responsible for the initial faster absorption (t_1/2a2= 1.99 h). Comparison of the area under the serum curves gave mean values of 117% for tetracycline and of 53% for chlortetracycline relative to oxytetracycline (arbitrarily fixed at 100%) after identical oral dosage of the three tetracyclines. We also propose and discuss a dosage schedule based on minimal inhibitory concentrations of different susceptible pathogens     

Pharmacokinetics of oxytetracycline in the American horseshoe crab, Limulus polyphemus

The American horseshoe crab, Limulus polyphemus, is regularly cultured and maintained in research laboratories and public aquaria. Rising concerns over the health of these captive animals makes the diagnosis and treatment of pathological conditions in L. polyphemus essential. This study investigated the kinetics of oxytetracyline following either intravascular or oral dosing. Oxytetracylcine is a broad-spectrum antibiotic used in the treatment of various bacterial diseases of aquatic animals. A noncompartmental model was developed to describe the pharmacokinetics of oxytetracycline (OTC) in the horseshoe crab. The following parameters were determined for a single intravascular bolus of 25 mg/kg OTC: AUC = 9524.60 microg.h/mL, MRT = 443.65 h, Clb = 0.044 mL/min/kg, Vd(ss) = 1.164 L/kg, t(1/2) = 128.3 h, Cmax = 55.90 microg/mL, C(ave) = 27.39 microg/mL. Following a single oral bolus of 25 mg/kg, these parameters were calculated: AUC = 5861.81 microg.h/mL, MRT = 395.89 h, Clb = 0.071 mL/min/kg, Vd(ss) = 1.688 L/kg, t(1/2) = 210.0 h, Cmax = 7.83 microg/mL, C(ave) = 2.89 microg/mL, F = 61.56%.     

Pharmacokinetics and local tolerance of a long-acting oxytetracycline formulation in camels.

Disposition and local tolerance of a new oxytetracycline (OTC) long-acting formulation were evaluated in camels by measuring the dynamics of creatine kinase. Six camels (Camelus dromedarius) were administered OTC by IV and IM routes according to a 2-period cross-over, study design. Serum OTC concentration was measured, using a microbiological assay procedure. After IV administration (5 mg/kg of body weight), mean residence time was 7.7 +/- 2.8 hours, steady-state volume distribution was 706.1 +/- 168.6 ml.kg-1 and serum clearance was 75.3 +/- 23.2 ml.kg-1.h-1. After IM administration of the long-acting OTC formulation (10 mg/kg), maximal OTC concentration (3.49 +/- 0.44 micrograms.ml-1) was observed after 7.3 +/- 3.5 hours; the mean systemic availability was near 100%, and serum concentration greater than 0.5 micrograms.ml-1 was maintained for about 72 hours. After IM administration, mean control serum activity of creatine kinase was multiplied by a factor of 3.36 +/- 1.55; at 72 hours after OTC administration, the serum creatine kinase activity returned to control values. It was concluded that OTC is an antibiotic of potential interest in camels and that a dosage regimen of 10 mg.kg-1 deserves attention when using a long-acting formulation that has good local tolerance and near total systemic availability.     

土霉素在斑节对虾体内药代动力学和生物利用度

在自然海水（盐度33）．水温为（28．0±1．0）℃养殖条件下,采用反相高效液相色谱法（RP—HPLC）,研究口灌（100mg／kg）和围心腔注射（20mg／kg）2种给药途径下,土霉素在斑节对虾（Penaeus7YlOylodoYl）体内的药代动力学和生物利用度。围心腔注射和口灌给药下,血药药时曲线均适合采用二室模型拟合。围心腔注射下血药达峰浓度（Cmax）、药时曲线下面积（AUC0-1）、消除半衰期（t,m）分别为（80．71±13．12）mg／L 378．25nag·h·L-1、17．398h;口灌给药下的相应值分别为（21．98±3．32）mg／I。324．52nag·h·L-1、23．372h,土霉素在斑节对虾体内的生物利用度（F）为17．16％。口灌土霉素后,肝胰腺Cmax为（138．655±21．375）μg／g,是血药的6．3倍、肌肉峰浓度的130．2倍,药物在肝胰腺中含量最高;然而。肌肉和肝胰腺中土霉素消除较快,消除半衰期（t1/2x）分别为28．18h和19．311 h。根据我国水产品中药物残留限量规定,水产品中土霉素的最高残留限量（NY5070—2002）为0．1mg／kg,结合本试验研究结果,斑节对虾使用土霉素后的休药期为5d,肌肉可食组织即符合无公害食品标准要求。     

Pharmacokinetics, urinary excretion and dosage regimen of levofloxacin following a single intramuscular administration in cross bred calves

The pharmacokinetics and urinary excretion following single intramuscular administration of levofloxacin at a dose of 4 mg/kg was investigated in seven male cross bred calves. Appreciable plasma concentration of levofloxacin (0.38 ± 0.06 µg/ml) was detected at 1 min after injection and the peak plasma level of 3.07 ± 0.08 µg/ml was observed at 1 h. The drug level above MIC₉₀ in plasma was detected up to 12 h after administration. Rapid absorption of the drug was also evident by the high value of the absorption rate constant (2.14 ± 0.24 /h). The overall systemic bioavailability of levofloxacin, after intramuscular administration, was 56.6 ± 12.4%. The high value of AUC (7.66 ± 0.72 mg . h/ml) reflected the vast area of body covered by drug concentration. Extensive distribution of the drug into various body fluids and tissues was noted by the high value of Vd_area (1.02 ± 0.05 l/kg). The high ratio of AUC/MIC (76.6 ± 7.25) obtained in this study indicated excellent clinical and bacteriological efficacy of levofloxacin in calves. The elimination half-life and MRT were 3.67 ± 0.4 h and 5.57 ± 0.51 h, respectively. The total body clearance (Cl_B) was 204.9 ± 22.6 ml/kg/h. On the basis of the pharmacokinetic parameters, a suitable intramuscular dosage regimen for levofloxacin in calves would be 1.5 mg/kg repeated at 12 h intervals.