Pharmacokinetics of Oleandomycin in Dogs After Intravenous or Oral Administration Alone and After Pretreatment With Metamizole or Dexamethasone

The pharmacokinetics of oleandomycin OLD) after intravenous and oral administration, both alone and after intramuscular pretreatment with metamizole or dexamethasone, were studied in healthy dogs. After intravenous injection of OLD alone 10 mg/kg as bolus), the elimination half-life t _1/2, volume of distribution V _{d, area}), body clearance CL_B) and area under the concentration-time curve AUC) were 1.60 h, 1.11 L/kg, 7.36 ml/kg)/min and 21.66 µg h/ml, respectively. There were no statistically significant differences following pretreatment with metamizole or dexamethasone. After oral administration of OLD alone, the t _frac12;, maximum plasma concentrations C _max), time of C _max t _max), mean absorption time MAT) and absolute bioavailability F _abs) were 1.68 h, 5.34 µg/ml, 1.5 h, 1.34 h and 84.29%, respectively. Pretreatment with metamizole caused a significantly decreased value for C _max 2.93 µg/ml) but the MAT value 2.23 h) was significantly increased. Statistically significant changes in the pharmacokinetic parameters of OLD following oral administration were also observed as a result of pretreatment with dexamethasone. The C _max was increased 8.24 µg/ml) and the t _max 0.5 h) and MAT 0.45 h) were lower.     

Monitoring C-reactive Protein in Beagle Dogs Experimentally Inoculated with Ehrlichia canis

The concentrations of C-reactive proteins (CRP) in the plasma of five beagle dogs experimentally inoculated with Ehrlichia canis increased markedly. The concentrations began to increase between 4 and 16 days and peaked between 15 and 42 days after inoculation of E. canis. The peak concentrations ranged from 217.8 to 788.8 g/ml (452.6±228.1 SD). After the peak, the concentrations of CRP decreased rapidly. The PCR product of 16S rRNA of E. canis became detectable in the five dogs between 18 and 27 days after inoculation of E. canis. Antibodies to E. canis were detected in plasma from the dogs between 5 and 15 days after inoculation of E. canis. The timings of seroconversion and of the start of the increase in CRP were approximately similar and the high concentrations of CRP in the plasma of the dogs tended to become apparent when the PCR product of 16 S rRNA of E. canis became detectable.     

Pharmacokinetics of Pefloxacin in Goats after Intravenous or Oral Administration

The plasma concentrations and pharmacokinetics of the fluoroquinolone antimicrobial agent pefloxacin, following the administration of a single intravenous (10 mg/kg) or oral (20 mg/kg) dose, were investigated in healthy female goats. The antimicrobial activity in plasma was measured at predetermined times after drug administration by an agar well diffusion microbiological assay, using Escherichia coli (ATCC 25922) as the test organism. Concentrations of the drug 0.25 g/ml were maintained in plasma for up to 6 and 10 h after intravenous (IV) or oral administration of pefloxacin, respectively. The concentration–time data for pefloxacin in plasma after IV or oral administration conformed to two- and one-compartment open models, respectively. Plasma pefloxacin concentrations decreased rapidly during the initial phase after IV injection, with a distribution half-life (t _1/2 ) of 0.10±0.01 h. The terminal phase had a half-life (t _1/2 ) of 1.12±0.21 h. The volume of distribution at steady state (V _dss), mean residence time (MRT) and total systemic clearance (Cl_B) of pefloxacin were 1.08±0.09 L/kg, 1.39±0.23 h and 821±88 (ml/h)/kg, respectively. Following oral administration of pefloxacin, the maximum concentration in the plasma (C _max) was 2.22±0.48 g/ml and the interval from administration until maximum concentration (t _max) was 2.3±0.7 h. The absorption half-life (t _{1/2 ka}), mean absorption time (MAT) and elimination half-life of pefloxacin were 0.82±0.40, 4.2±1.0 and 2.91±0.50 h, respectively. The oral bioavailability of pefloxacin was 42%±5.8%. On the basis of the pharmacokinetic data, a dosage regimen of 20 mg/kg, IV at 8 h intervals or orally twice daily, is suggested for treating infections caused by drug-sensitive pathogens in goats.     

Comparative pharmacokinetics of orbifloxacin in healthy and Pasteurella multocida infected ducks

1. The pharmacokinetic aspects of orbifloxacin were studied in both healthy and naturally diseased ducks after a single intravenous and intramuscular dose of 5?mg?kg^?1 body weight. The serum concentrations of orbifloxacin following single intravenous and intramuscular injections were higher in diseased than in healthy ducks.

2. The disposition of orbifloxacin after a single intravenous injection was described by a two-compartment open model in both healthy and diseased ducks. Orbifloxacin was distributed and eliminated at a significantly slower rate in diseased than in healthy ducks. The total body clearance (Cl_B) was lower in diseased (0·131?l?kg^?1?h^?1) than healthy ducks (0·191?l?kg^?1?h^?1).

3. Following intramuscular administration of orbifloxacin, the peak serum concentration (C_max) was higher in diseased than in healthy ducks, and this was achieved at a maximum time (t_max) of 1·114 and 0·993?h, respectively. The drug was eliminated at a significant slower rate in diseased ducks (elimination half-life t _{0·5( el )?}=?5·07?h) than in healthy ducks (elimination half-life t _{0·5( el )?}=?4·18?h).

4. These results indicate that drug elimination patterns in healthy and diseased ducks are not the same. The pharmacokinetic profile of the drug is altered in diseased ducks due to the increased serum orbifloxacin concentrations compared with clinically healthy ducks. In conclusion, 5?mg?kg^?1 body weight of orbifloxacin administered as a single dose once daily could be useful in the treatment of disease caused by Pasteurella multocida pathogen in ducks.     

Some Pharmacokinetic Parameters of Pefloxacin in Lactating Goats

The aim of this study was to elucidate some of the pharmacokinetic parameters of pefloxacin in lactating goats (n = 5) following intravenous (i.v.) or intramuscular (i.m.) injections of 10 mg/kg bw. Serially obtained serum, milk and urine samples were collected at precise time intervals, and the drug concentrations were assayed using a microbiological assay. A two-compartment open model best described the decrease of pefloxacin concentration in the serum after intravenous administration. The maximum serum concentration (C _p ⁰ ) was 8.4±0.48 g/ml; elimination half-life (t _1/2) was 1.6±0.3 h; total body clearance (Cl_tot) was 3.6±0.3 L/kg/h; steady-state volume of distribution (V _dss) was 5.14±0.21 L/kg; and the area under the curve (AUC) was 2.78±0.22 g.ml/h. Pefloxacin was absorbed rapidly after i.m. injection with an absorption half-life (t _1/2ab) of 0.32±0.02 h. The peak serum concentration (C _max) of 0.86±0.08 g/ml was attained at 0.75 h (T _max). The absolute bioavailability after i.m. administration was 70.63±1.13% and the serum protein-bound fraction ranged from 7.2% to 14.3%, with an average value of 9.8±1.6%. Penetration of pefloxacin from the blood into the milk was rapid and extensive, and the pefloxacin concentration in milk exceeded that in serum from 1 h after administration. The drug was detected in milk and urine for 10 and 72 h, respectively; no samples were taken after 72 h.     

The pharmacokinetics of thiamphenicol in lactating cows

The pharmacokinetics of thiamphenicol were studied after intravenous and intramuscular administration of 25 mg/kg body weight in lactating cows. Distribution (t _1/2) and elimination (t _1/2) half-lives of 6.10±1.39 min and 1.60±0.30 h, respectively, were obtained after intravenous administration. The body clearance was 3.9±0.077 ml/kg per min and the apparent volume of distribution was 1220.79±256.67 ml/kg. The rate at which thiamphenicol appeared in the milk, as indicated by the penetration half-life (t _1/2P) (serum to quarters), was found to be 36.89±11.14 min. The equivalent elimination half-life (t _1/2E) (quarters to serum) from the milk was 3.62±1.06 h and the peak thiamphenicol concentration in the milk was 23.09±3.42 µg/ml at 2.5±0.32 h.After intramuscular injection, the elimination half-life was 2.2±0.40 h, the absorption half-life was 4.02±1.72 min and the peak concentration in the serum was 30.90±5.24 µg/ml at 23±8.4 min. The bioavailability after intramuscular administration approached 100%. The penetration half-life was 50.59±6.87 min, the elimination half-life was 5.91±4.97 h and the mean peak concentration in the milk was 17.37±2.20 µg/ml at 3.4±0.22 h.Abbreviations AUC area under the concentration-time curve - CAP chloramphenicol - C _max peak concentration - IM intramuscular - IV intravenous - TAP thiamphenicol - t _1/2 distribution half-life - t _1/2 elimination half-life - V _c volume of central compartment - V _d volume of distribution     

Pulmonary Hypertension Induced in Dogs by Hypoxia at Different High-Altitude Levels

Chronic natural hypoxia at 2300 m altitude induces mild pulmonary hypertension (PH) in healthy dogs. The influence of more severe hypoxia on the same group of dogs was evaluated by re-examining such dogs at 3500 m, after they had regularly exercised at this altitude level for half a year. Despite severe hypoxaemia at 3500 m (P _aO₂ 52±5 mmHg), none of the dogs developed erythrocytosis, and their PCV at 3500 m (48%±4%) did not differ from that at 2300 m (49%±4%). There was a tendency towards an elevated systemic BP, with a significant increase in diastolic BP (105±13 mmHg at 3500 m versus 98±17 at 2300 m). Tricuspid regurgitation (TR) was detected in 7 dogs at 3500 m compared to 8 dogs at 2300 m. The mean TR V _max was significantly higher at 3500 m, and all 7 dogs had systolic PH at 3500 m (33.6–54.8 mmHg), when PH was defined as TR V _max 2.8 m/s, i.e. a peak pressure gradient >30 mmHg. Hence, in dogs, increasing altitude and the concomitant hypoxia result in a progressively more pronounced PH and an elevated systemic BP. Intermittent severe hypoxaemia of around 50 mmHg may not cause erythrocytosis in healthy dogs, even over a prolonged period.     

The influence of Trypanosoma congolense infection on the disposition kinetics of diminazene aceturate in the dog

Diminazene aceturate was administered intravenously at 3.5 mg/kg body weight to mongrel dogs before and after infection with Trypanosoma congolense. Plasma and urine were collected at varying intervals thereafter and analysed for the compound. The mean are under the concentration-time curve (AUC) of diminazene in healthy dogs was 25.8 h.g/ml but was significantly increased (p<0.05) to 35.7 h.g/ml after infection with T. congolense. The distribution half-life was significantly reduced (p<0.05) in dogs after infection, being 0.12 h compared to 0.17 h in the same dogs before infection. The mean proportion of the diminazene recovered in the urine of infected dogs (25.1%) was not significantly different from that recovered in the urine of healthy dogs (26.8%). These results indicate that infection with T. congolense increases the rate at which diminazene is distributed in the body but that the infection has no marked influence on the urinary excretion of the drug.     

Investigation of pharmacokinetic interaction between ivermectin and praziquantel after oral administration in healthy dogs

The purpose of this study was to determine the pharmacokinetic interaction between ivermectin (0.4 mg/kg) and praziquantel (10 mg/kg) administered either alone or co‐administered to dogs after oral treatment. Twelve healthy cross‐bred dogs (weighing 18–21 kg, aged 1–3 years) were allocated randomly into two groups of six dogs (four females, two males) each. In first group, the tablet forms of praziquantel and ivermectin were administered using a crossover design with a 15‐day washout period, respectively. Second group received tablet form of ivermectin plus praziquantel. The plasma concentrations of ivermectin and praziquantel were determined by high‐performance liquid chromatography using a fluorescence and ultraviolet detector, respectively. The pharmacokinetic parameters of ivermectin following oral alone‐administration were as follows: elimination half‐life (t_1/2λz) 110 ± 11.06 hr, area under the plasma concentration–time curve (AUC_0–∞) 7,805 ± 1,768 hr^.ng/ml, maximum concentration (C_max) 137 ± 48.09 ng/ml, and time to reach C_max (T_max) 14.0 ± 4.90 hr. The pharmacokinetic parameters of praziquantel following oral alone‐administration were as follows: t_1/2λz 7.39 ± 3.86 hr, AUC_0–∞ 4,301 ± 1,253 hr^.ng/ml, C_max 897 ± 245 ng/ml, and T_max 5.33 ± 0.82 hr. The pharmacokinetics of ivermectin and praziquantel were not changed, except T_max of praziquantel in the combined group. In conclusion, the combined formulation of ivermectin and praziquantel can be preferred in the treatment and prevention of diseases caused by susceptible parasites in dogs because no pharmacokinetic interaction was determined between them.     

Pharmacokinetics of allopurinol in Dalmatian dogs

The pharmacokinetics of allopurinol were studied in Dalmatian dogs. Eight dogs were given allopurinol orally at a dose of 10 mg/kg for seven doses prior to sample collection. After a period of at least two weeks, four of these dogs and four additional Dalmatians were later given a single intravenous (i.v.) dose of allopurinol (6 mg/kg) prior to sample collection.Allopurinol was found to follow first-order absorption and elimination kinetics. In the i.v. kinetic study, the elimination constant (K_el) = 0.31±0.03 per h, the half-life (t_½) = 2.22±0.20 h, the initial concentration (C₀) = 5.26±0.34 μg/mL and the specific volume (V_d) = 1.14±0.07 L/kg. Clearance of allopurinol was estimated to be 0.36±0.03 L/kg·h. In the oral kinetic study, the absorption rate constant (K_ab) = 1.06±0.13 per h, the elimination rate constant (K_el) = 0.26±0.01 per h, the absorption half-life (t_½ab) = 0.66±0.06 h, and the elimination half-life (t_½el) = 2.69±0.14 h. Peak plasma concentrations (C_max) = 6.43±0.18 μg/mL were obtained within 1 to 3 h (mean time of maximum concentration (T_max) = 1.9±0.1 h). The volume of distribution corrected by the fraction of dose absorbed (V_d/F) was estimated to be 1.17±0.07 L/kg.Good agreement was obtained between mean kinetic parameters in the oral and i.v. studies. There was little variation between individual dogs in the i.v. study, whereas the rate of absorption and elimination of orally administered allopurinol was more varied among individual dogs. Because of this, and the fact that the magnitude of hyperuricosuria varies among Dalmatians, it is not possible to specify an exact dose of allopurinol that will effectively lower the urinary uric acid concentration to acceptable values in all Dalmatians with hyperuricosuria; rather, the dose must be titrated to the needs of each dog.     

The pharmacokinetics of a slow-release theophylline preparation in horses after intravenous and oral administration

The pharmacokinetics of a slow-release theophylline formulation was investigated following intravenous and oral administration at 10 mg/kg in horses. A tricompartmental model was selected to describe the intravenous plasma profile. The elimination half-life (t1/2) was 16.91 ± 0.93 h, the apparent volume of distribution (V _d) was 1.35 ± 0.18 L/kg and the body clearance (Cl_B) was 0.061 ± 0.009 L kg^–1 h. After oral administration the half-life of absorption was 1.24 ± 0.30 h, and the calculated bioavailability was above 100%. Thet1/2 after oral administration was 18.51 ± 1.75 h, only a little longer than that after intravenous administration. The slow release formulation did not exhibit any advantage in prolonging thet1/2 of theophylline in the horse.     

Pharmacokinetics of thiamphenicol in Japanese quails (Coturnix japonica) after single intravenous and oral administrations

Thiamphenicol (TP) pharmacokinetics were studied in Japanese quails (Coturnix japonica) following a single intravenous (IV) and oral (PO) administration at 30 mg/kg BW. Concentrations of TP were determined with HPLC and were analyzed by a noncompartmental method. After IV injection, elimination half-life (t_1/2λz), total body clearance (Cl_tot) volume of distribution at steady state (V_dss), and mean residence time (MRT) of TP were 3.83 hr, 0.19 L/hr/kg, 0.84 L/kg, and 4.37 hr, respectively. After oral administration of TP, the peak plasma concentration (C_max) was 19.81 μg/ml and was obtained at 2.00 hr (t_max) postadministration. Elimination half-life (t_1/2λz) and mean absorption time (MAT) were 4.01 hr and 1.56 hr, respectively. The systemic bioavailability following oral administration of TP was 78.10%. TP therapy with an oral dosage of 30 mg/kg BW is suggested for a beneficial clinical effect in quails.     

Pharmacokinetics of ceftiofur sodium in Peekapoo dogs following a single intravenous and subcutaneous injection

The present study aimed to determine the pharmacokinetic profiles of ceftiofur (as measured by ceftiofur and its active metabolites concentrations) in a small-size dog breed, Peekapoo, following a single intravenous or subcutaneous injection of ceftiofur sodium. The study population comprised of five clinically healthy Peekapoo dogs with an average body weight (BW) of 3.4 kg. Each dog received either intravenous or subcutaneous injection, both at 5 mg/kg BW (calculated as pure ceftiofur). Plasma samples were collected at different time points after the administration. Ceftiofur and its active metabolites were extracted from plasma samples, derivatized, and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetic parameters. The terminal half-life (t_1/2λz) was calculated as 7.40 ± 0.79 and 7.91 ± 1.53 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (V_SS) were determined as 39.91 ± 4.04 ml hr⁻¹ kg⁻¹ and 345.71 ± 28.66 ml/kg, respectively. After subcutaneous injection, the peak concentration (C_max; 10.50 ± 0.22 μg/ml) was observed at 3.2 ± 1.1 hr, and the absorption half-life (t_1/2ka) and absolute bioavailability (F) were calculated as 0.74 ± 0.23 hr and 91.70%±7.34%, respectively. The pharmacokinetic profiles of ceftiofur and its related metabolites demonstrated their quick and excellent absorption after subcutaneous administration, in addition to poor distribution and slow elimination in Peekapoo dogs. Based on the time of concentration above minimum inhibitory concentration (T > MIC) values calculated here, an intravenous or subcutaneous dose at 5 mg/kg of ceftiofur sodium once every 12 hr is predicted to be effective for treating canine bacteria with a MIC value of ≤4.0 μg/ml.     

Comparative Plasma Pharmacokinetics and Tolerance of Florfenicol following Intramuscular and Intravenous Administration to Camels,Sheep and Goats

Florfenicol, a monofluorinated analogue of thiamphenicol, has a broad antibacterial spectrum. The pharmacokinetics of florfenicol was studied following a single intravenous (i.v.) or intramuscular (i.m.) injection at a dose of 20 mg/kg body weight in healthy male camels, sheep and goats. The concentration of florfenicol in plasma was determined using a microbiological assay. Pharmacokinetic analysis was performed using a two-compartment open model. Following i.m. administration, the maximum plasma concentration of florfenicol (C _max) reached in camels, sheep and goats was 0.84±0.08, 1.04±0.10 and 1.21±0.10 g/ml, respectively, the the time required to reach C _max (t _max) in the same three respective species was 1.51±0.14, 1.44±0.10 and 1.21±0.10 h. The terminal half-life (t _1/2) and the fraction of the drug absorbed (F%) in camels, sheep and goats were 151.3±16.33, 137.0±12.16 and 127.4±11.0 min, and 69.20%±7.8%, 65.82%±6.7% and 60.88%±5.9%, respectively. The MRT in the same three respective species was 4.01±0.45, 3.42±0.39 and 2.98±0.32 h. Following i.v. administration, the terminal half-life (t _1/2) and total body clearance (Cl_B) in camels, sheep and goats were 89.5±9.2, 78.8±8.3 and 71.1±8.9 min and 0.33±0.04, 0.30±0.03 and 0.27±0.03 L/h per kg, respectively. The area under the curve (AUC_0–) and the mean residence time (MRT) in the same three respective species were 60.61±6.98, 62.45±6.56 and 74.07±7.85 g/ml per h, and 2.71±0.31, 2.34±0.25 and 2.11±0.23 h. These data suggest that sheep and goats absorb and clear florfenicol to a broadly similar extent, but the rate and extent of absorption of the drug tends to be higher in camels. Drug treatment caused no clinically overt adverse effects. Plasma enzyme activities and metabolites indicative of hepatic and renal functions measured 1, 2, 4 and 7 days following the drug treatment were within the normal range, indicating that the drug is safe at the dose used.     

Pharmacokinetics of Total Thyroxine after Repeated Oral Administration of Levothyroxine Solution and its Clinical Efficacy in Hypothyroid Dogs

Background

Oral levothyroxine (l‐T₄) supplementation is commonly used to treat hypothyroid dogs.

Objectives

Investigate the plasma profile and pharmacokinetics of total thyroxine (tT₄) after PO administration of a l‐T₄ solution and its clinical efficacy in hypothyroid dogs.

Animals

Ten dogs with naturally occurring hypothyroidism.

Methods

After hypothyroidism diagnosis and supplementation with l‐T₄ solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT₄ were determined over 34 hours and the clinical condition of the dogs was evaluated.

Results

Before dosing for pharmacokinetic evaluation, mean tT₄ concentration was 23 ± 9 nmol/L. l‐T₄ was absorbed rapidly (t _max, 5 hours), reaching a mean maximal tT₄ concentration of 56 ± 11 nmol/L. The apparent terminal half‐life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9–16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog.

Conclusions and Clinical Importance

The pharmacokinetics of l‐T₄ in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l‐T₄ solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog.     

Bioavailability and pharmacokinetic profile of levofloxacin following intravenous,intramuscular and oral administration in turkeys

1. The pharmacokinetics and bioavailability of levofloxacin in turkeys were investigated after a single intravenous (IV), intramuscular (IM) and oral (PO) administration of 10 mg/kg body weight.

2. The concentrations of levofloxacin in plasma samples were assayed using a microbiological assay method and pharmacokinetic parameters were calculated by non-compartmental analysis.

3. Following IV administration, the elimination half-life (t_0.5(β)), volume of distribution at steady state (Vd_ss) and total body clearance (Cl) were 4.49 h, 1.31 l/kg and 0.23 l/h/kg, respectively.

4. After single IM and PO administrations at the same dose, levofloxacin was rapidly absorbed as indicated by an absorption half-life (t_0.5ab) of 1.02 and 0.76 h, respectively; maximum plasma concentrations (C_max) of 5.59 and 5.15 μg/ml were obtained at a maximum time (T_max) of 2 h for both routes and levofloxacin bioavailability (F) was 96.5 h and 79.9% respectively after IM and PO administration. In vitro plasma protein binding of levofloxacin was 24.3%.

5. Based on these pharmacokinetic parameters, a dose of 10 mg/kg body weight given intramuscularly or orally every 24 h in turkeys can maintain effective plasma concentrations with bacterial infections with (minimum inhibitory concentration) MIC₉₀ > 0.1 μg/ml.     

The pharmacokinetics of ceftazidime in lactating and non-lactating cows

The pharmacokinetics of ceftazidime (CAZ) were studied in lactating (LTG) and non-lactating (NLTG) cows. Two groups (LTG and NLTG) of 5 healthy dairy cows were given ceftazidime (10 mg/ kg body weight) intravenously (i.v.) and intramuscularly (i.m.). Serum and milk (LTG) and serum samples (NLTG) were collected over a 24-h period post-administration. CAZ concentrations in serum and milk were determined by high-performance liquid chromatography, and an interactive and weighted-non-linear least-squares regression analysis was used to perform the pharmacokinetic analysis. The pharmacokinetic profiles in LTG and NLTG cows which had received CAZ i.v. fitted a three-compartment model and a two-compartment model, respectively. The CAZ concentration-time curves in serum and the area under the curve were greater and more sustained (p<0.05) in the LTG cows by both routes, while the serum clearance (Cl_s=72.5±18.1 ml/h per kg) was lower (p<0.05) than that in the NLTG cows (Cl_s=185.9±44.2 ml/h per kg). CAZ given i.v. exhibited a relatively long half-life of elimination (t _1/2 (LTG)=1.1±0.2 h; t _1/2 (NLTG)=1.4±0.3 h). Compared with other cephalosporins, CAZ had good penetration into the mammary gland (47.7±38.2% for CAZ i.v.; 51.1±39.0% for CAZ i.m.). Finally, the bioavailability of CAZ (F(LTG)=98.9±36.8%; F(NLTG)=77.1±25.3%) was suitable for its use by the i.m. route in lactating and non-lactating cows.Abbreviations AIC Akaike information criterion - AUC area under the curve - b.w. body weight - CAZ ceftazidime - Cl_s total serum clearance - C _max peak serum concentration - COM compartment open model - i.m. intramuscular(ly) - i.v. intravenous(ly) - LTG lactating - K rate constant - 1 central compartment - 2 peripheral compartment - 3 deep compartment - NLTG nonlactating - t _max time of peak serum concentration - t _1/2 half-life     

Pharmacokinetics of doxycycline in laying hens after intravenous and oral administration

1. The pharmacokinetics of doxycycline in laying hens was investigated after a single intravenous (IV) or an oral (PO) dose at 20 mg/kg body weight.

2. The concentrations of doxycycline in plasma samples were determined by high-performance liquid chromatography with an ultraviolet detector, and pharmacokinetic parameters were calculated using a compartmental model method.

3. The disposition of doxycycline after one single IV injection was best described by a two-compartment open model and the main pharmacokinetic parameters were as follows: volume of distribution (V_d) was 865.15 ± 127.64 ml/kg, distribution rate constant (α) was (2.28 ± 0.38) 1/h, elimination rate constant (β) was 0.08 ± 0.02 1/h and total body clearance (Cl) was104.11 ± 18.32 ml/h/kg, while after PO administration, the concentration versus time curve was best described by a one-compartment open model and absorption rate constant (K_a), peak concentration (C_max), time to reach C_max (t_max) and absolute bioavailability (F) were 2.55 ± 1.40 1/h, 5.88 ± 0.70 μg/ml, 1.73 ± 0.75 h and 52.33%, respectively.

4. The profile of doxycycline exhibited favourable pharmacokinetic characteristics in laying hens, such as quick absorption and slow distribution and elimination, though oral bioavailability was relatively low. A multiple-dosing regimen (a dose of 20 mg/kg/d for 3 consecutive days) of doxycycline was recommended to treat infections in laying hens. But a further study should be conducted to determine the withdrawal time of doxycycline in eggs.

     

Pharmacokinetics of cefpodoxime in plasma and subcutaneous fluid following oral administration of cefpodoxime proxetil in male beagle dogs

Kumar, V., Madabushi, R., Lucchesi, M. B. B., Derendorf, H. Pharmacokinetics of cefpodoxime in plasma and subcutaneous fluid following oral administration of cefpodoxime proxetil in male beagle dogs. J. vet. Pharmacol. Therap. 34 , 130–135. Pharmacokinetics of cefpodoxime in plasma (total concentration) and subcutaneous fluid (free concentration using microdialysis) was investigated in dogs following single oral administration of prodrug cefpodoxime proxetil (equivalent to 5 and 10 mg/kg of cefpodoxime). In a cross over study design, six dogs per dose were utilized after a 1 week washout period. Plasma, microdialysate, and urine samples were collected upto 24 h and analyzed using high performance liquid chromatography. The average maximum concentration (C_max) of cefpodoxime in plasma was 13.66 (±6.30) and 27.14 (±4.56) μg/mL with elimination half‐life (t_1/2) of 3.01 (±0.49) and 4.72 (±1.46) h following 5 and 10 mg/kg dose, respectively. The respective average area under the curve (AUC_0–∞) was 82.94 (±30.17) and 107.71 (±30.79) μg·h/mL. Cefpodoxime was readily distributed to skin and average free C_max in subcutaneous fluid was 1.70 (±0.55) and 3.06 (±0.93) μg/mL at the two doses. Urinary excretion (unchanged cefpodoxime) was the major elimination route. Comparison of subcutaneous fluid concentrations using pharmacokinetic/pharmacodynamic indices of fT_>MIC indicated that at 10 mg/kg dose; cefpodoxime would yield good therapeutic outcome in skin infections for bacteria with MIC₅₀ upto 0.5 μg/mL while higher doses (or more frequent dosing) may be needed for bacteria with higher MICs. High urine concentrations suggested cefpodoxime use for urinary infections in dogs.     

Some pharmacokinetic parameters of doxycycline in East African goats after intramuscular administration of a long-acting formulation

A compartmental and non-compartmental study was carried out on five adult goats following intramuscular administration of doxycycline at 20 mg/kg bodyweight. The concentration of the drug in serum was determined by a microbiological assay employingBacillus cereus varmycoides (ATCC 11778) as the test organism. The mean serum concentration (C _max) and the time of maximum concentration (T _max) were 1.87 µg/ml and 0.85 h, respectively. Using compartmental analysis, the plasma concentration-time curve of doxycycline best fitted a three-compartment open model with first-order absorption. A three-phase disposition of doxycycline was found, the terminal elimination half-life being approximately 40 h.The statistical moment theory was mainly used for non-compartmental analysis. The value obtained for the mean residence time (MRT) was 16.41 h. The mean values for the volume of distribution at steady state (V _dss), determined by compartmental and non-compartmental analyses, were 8.73 and 13.19 L/kg, respectively. There were no statistically significant differences when the major pharmacokinetic parameters were compared.It was concluded that the pharmacokinetic behaviour of doxycycline in goats after intramuscular administration is characterized by a three-compartment model with a slow terminal elimination phase. Based on current knowledge, this could be due to enterohepatic recycling and/or flip-flop kinetics. The study indicated that a single intramuscular administration of 20 mg/kg of doxycycline may only provide therapeutic concentrations for up to 24 h owing to slow absorption at the injection site.Abbreviations ATCC American Type Culture Collection - AVC total area under the plasma concentration-time curve - AUMC area under the curve of the product from time zero to infinity - C1 total body clearance - i.m. intramuscular - i.v. intravenous - MRT mean residence time - MIC minimum inhibitory concentration - PVP polyvinyl pyrolidone - V_d volume of distribution - V _dss volume of distribution at steady state