Pharmacokinetics of thiamylal in cats

Pharmacokinetics of thiamylal were determined after 13.2 mg of thiamylal/kg of body weight was administered IV to 6 healthy cats. Blood samples were obtained for 12 hours. Disposition of thiamylal best conformed to 2 multicompartmental models, a 2-compartment (n = 1) and a 3-compartment (n = 5) open pharmacokinetic model. The pharmacokinetic values were calculated for the overall best-fitted model, a mixed 2- and 3-compartmental model. The first or rapid distribution half-life was 1.91 minutes and a second, or slower, distribution half-life was 26.51 minutes. The elimination half-life was 14.34 hours. The apparent volume of distribution was 3.61 +/- 1.8463 L/kg, whereas the apparent volume of the central compartment was 0.46 +/- 0.2034 L/kg, and the total clearance was 0.135 +/- 0.0616 L/kg/h.     

Single- and repeat-dose pharmacokinetic studies of chloramphenicol in horses: values and limitations of pharmacokinetic studies in predicting dosage regimens

A single-dose pharmacokinetic study of chloramphenicol in propylene glycol was done in 6 horses after 22 mg/kg was administered IV. Serum drug concentrations obtained at various predetermined intervals were determined by an electroncapture gas-chromatographic technique. The time-concentration data were described by a 2-compartment open model, and various pharmacokinetic variables were estimated. The median elimination rate constant was estimated to be -0.0185 minute-1 (-0.0225 to -0.0148 minute-1), and the median half-life was 37.36 minutes (30.74 to 46.90 minutes). The median apparent volume of distribution and total body clearance were 1.46 L/kg (1.13 to 1.60 L/kg) and 25.56 ml/kg/min (23.66 to 32.21 ml/kg/min), respectively. On the basis of these data, single- and repeat-dose kinetic studies were done in another group of 6 animals. The drug was administered at a dosage of 22 mg/kg every 4 hours for 3 days. Blood samples were obtained for pharmacokinetic studies after the first and the last doses were given. The half-life, volume of distribution, and total body clearance did not change significantly (Wilcoxon signed rank test) after 3 days of therapy with chloramphenicol. The IV dose schedule for treating bacterial infections with organisms of different sensitivities has been determined from the estimates of the pharmacokinetic variables. The limitations of calculating the dose schedules for chloramphenicol on the basis of pharmacokinetic variables in horses are discussed.     

Pharmacokinetics of flunixin meglumine in dogs

The pharmacokinetics of flunixin meglumine, a potent nonsteroidal anti-inflammatory agent, were studied in 6 intact, awake dogs. Plasma samples were obtained up to 12 hours after IV administration of flunixin meglumine. Flunixin concentration was determined, using high performance liquid chromatography. Plasma data best fit a 2-compartment model. Distribution half-life was 0.55 hour; elimination half-life was 3.7 hours; volume of distribution (area) was 0.35 L/kg; volume of distribution at steady state was 0.18 L/kg; volume of the central compartment was 0.079 L/kg; and total body clearance was 0.064 L/hr/kg. Flunixin concentrations obtained over a 6-hour period in 3 dogs with septic peritonitis did not differ significantly from those obtained from healthy dogs.     

Pharmacokinetics of pipemidic acid in chickens after single intravenous and oral dosings

The pharmacokinetics of pipemidic acid after 2 single doses were studied in broiler chickens. Chickens were given single IV and oral doses of 10 and 30 mg of pipemidic acid/kg of body weight. Blood samples were collected over 8 hours after each dose administration. High-pressure liquid chromatography with UV detection was used to determine concentrations in plasma of pipemidic acid. The plasma concentration-time curves after IV administration followed 2-compartment characteristics, rapid initial distribution phase, and a terminal elimination phase. The pharmacokinetic variables differed significantly between single doses of 10 and 30 mg of pipemidic acid/kg. Mean disposition variables were a half-life at alpha phase of 0.06 hours or 0.33 hours, a half-life at beta phase of 1.18 hours or 1.72 hours, a volume of distribution in the central compartment of 0.12 L/kg or 0.31 L/kg, a volume of distribution during the elimination beta phase of 1.64 L/kg or 1.05 L/kg, and a total plasma clearance of 0.97 L/h.kg or 0.41 L/h.kg, for the 10 or 30 mg/kg dose, respectively. After oral administration, the pipemidic acid plasma profile could be adequately described by a 1-compartment model. After the single oral doses of 10 and 30 mg of pipemidic acid/kg, pipemidic acid was absorbed rapidly (time to maximal concentration of 0.31 hours or 0.71 hours) and eliminated with a mean half-life of 0.86 hours or 0.61 hours, respectively. The bioavailability was 39% at 10 mg of pipemidic acid/kg and 61% at 30 mg of pipemidic acid/kg.     

Pharmacokinetics of intravenously and orally administered pyrimethamine in horses.

Single-dose pharmacokinetic variables of pyrimethamine were studied in horses. Pyrimethamine (1 mg/kg of body weight) was administered IV and orally to 6 adult horses, and plasma samples were obtained at frequent intervals thereafter. Plasma pyrimethamine concentration was assayed by gas chromatography, and concentration-time data were analyzed, using a pharmacokinetic computer program. The IV and oral administration data were best described by 3-compartment and 1-compartment models, respectively. The median volume of distribution at steady state after IV administration was 1,521 ml/kg and the median elimination half-time was 12.06 hours. Mean plasma concentration after oral administration fluctuated between a maximal concentration of 0.18 microgram/ml and 0.09 microgram/ml (24 hours after dosing). Bioavailability after oral administration was 56%.     

Pharmacokinetics of butorphanol tartrate in rabbits.

The pharmacokinetic properties of butorphanol tartrate were determined in 7 rabbits after IV and SC injection (0.5 mg/kg of body weight). A 2-compartment model (biexponential) best represented the concentration vs time curve after IV injection. The half-life was calculated to be 1.64 hours via IV administration, whereas SC injection resulted in an elimination half-life of 3.16 hours.     

Compartmental and noncompartmental pharmacokinetic analyses of minocycline hydrochloride in the dog

Six adult dogs were given 5 mg of minocycline hydrochloride/kg of body weight IV. Pharmacokinetic evaluation of the serum drug concentration versus time data was performed, using the 2-compartment open model, the 3-compartment open model, and a noncompartmental model involving use of the statistical moment theory. All pharmacokinetic values except clearance were model independent. Minocycline half-life ranged between 6.48 and 7.24 hours; volume of distribution at steady state, between 1.859 +/- 0.368 and 2.001 +/- 0.468 L/kg; and clearance, between 3.195 +/- 0.618 and 3.424 +/- 0.684 ml/min/kg. These data are similar to those reported for oxytetracycline and indicate that the frequency of administration of the 2 tetracyclines should be the same. Three of the 6 dogs developed an adverse response to the IV injection of minocycline. Dog 1 developed urticaria and had initial serum drug concentrations of approximately 2 times the mean concentrations for the other dogs; values were not included in the pharmacokinetic analysis. Two other dogs had transient signs indicating cardiovascular depression or hypotension; their data were included. Due to the frequency of the unexpected reactions found in this study, it was concluded that dogs should not be given minocycline rapidly IV.     

Evaluation of the bioavailability and pharmacokinetics of two extended-release theophylline formulations in dogs

OBJECTIVE: To evaluate the bioavailability and pharmacokinetic characteristics of 2 commercially available extended-release theophylline formulations in dogs. DESIGN: Randomized 3-way crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURE: A single dose of aminophylline (11 mg x kg(-1) 15 mg x lb(-1)], i.v., equivalent to 8.6 mg of theophylline/kg 13.9 mg x lb(-1) or extended-release theophylline tablets (mean dose, 15.5 mg x kg(-1) [7.04 mg x lb9-1), PO) or capsules (mean dose, 15.45 mg x kg(-1) [7.02 mg x lb(-1)], PO) was administered to all dogs. Blood samples were obtained at various times for 36 hours after dosing; plasma was separated and immediately frozen. Plasma samples were analyzed by use of fluorescence polarization immunoassay. RESULTS: Administration of theophylline i.v. best fit a 2-compartment model with rapid distribution followed by slow elimination. Administration of extended-release theophylline tablets and capsules best fit a 1-compartment model with an absorption phase. Mean values for plasma terminal half-life, volume of distribution, and systemic clearance were 8.4 hours, 0.546 L x kg(-1), and 0.780 mL x kg(-1) x min(1), respectively, after i.v. administration of theophylline. Systemic availability was > 80% for both oral formulations. Computer simulations predicted that extended-release theophylline tablets or capsules administered at a dosage of 10 mg x kg(-1) (4.5 mg x lb(-1)), PO, every 12 hours would maintain plasma concentrations within the desired therapeutic range of 10 to 20 microg x mL(-10. CONCLUSIONS AND CLINICAL RELEVANCE: Results of these single-dose studies indicated that administration of the specific brand of extended-release theophylline tablets or capsules used in this study at a dosage of 10 mg x kg(-1), PO, every 12 hours would maintain plasma concentrations within the desired therapeutic range (10 to 20 microg x mL(-1)) in healthy dogs.     

Pharmacokinetics and effects of aminorex in horses

OBJECTIVE: To investigate the pharmacokinetics and behavioral effects of aminorex administered IV and PO in horses. ANIMALS: 7 Thoroughbreds. PROCEDURES: In a cross-over design, aminorex (0.03 mg/kg) was administered IV or PO. Plasma and urinary aminorex concentrations were determined via liquid chromatography- mass spectrometry. RESULTS: Decrease of aminorex from plasma following IV administration was described by a 3-compartment pharmacokinetic model. Median (range) values of alpha, beta, and gamma half-lives were 0.04 (0.01 to 0.28), 2.30 (1.23 to 3.09), and 18.82 (8.13 to 46.64) hours, respectively. Total body and renal clearance, the area under the plasma time curve, and initial volume of distribution were 37.26 (28.61 to 56.24) mL x min/kg, 1.25 (0.85 to 2.05) mL x min/kg, 13.39 (8.82 to 17.37) ng x h/mL, and 1.44 (0.10 to 3.64) L/kg, respectively. Oral administration was described by a 2-compartment model with first-order absorption, elimination from the central compartment, and distribution into peripheral compartments. The absorption half-life was 0.29 (0.12 to 1.07) hours, whereas the beta and gamma elimination phases were 1.93 (1.01 to 3.17) and 23.57 (15.16 to 47.45) hours, respectively. The area under the curve for PO administration was 10.38 (4.85 to 13.40) ng.h/mL and the fractional absorption was 81.8% (33.8% to 86.9%). CONCLUSIONS AND CLINICAL RELEVANCE: Aminorex administered IV had a large volume of distribution, initial rapid decrease, and an extended terminal elimination. Following PO administration, there was rapid absorption, rapid initial decrease, and an extended terminal elimination. At a dose of 0.03 mg/kg, the only effects detected were transient and central in origin and were observed only following IV administration.     

Plasma pharmacokinetics and tissue fluid concentrations of meropenem after intravenous and subcutaneous administration in dogs

OBJECTIVE: To estimate pharmacokinetic variables and measure tissue fluid concentrations of meropenem after IV and SC administration in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURE: Dogs were administered a single dose of meropenem (20 mg/kg) IV and SC in a crossover design. To characterize the distribution of meropenem in dogs and to evaluate a unique tissue fluid collection method, an in vivo ultrafiltration device was used to collect interstitial fluid. Plasma, tissue fluid, and urine samples were analyzed by use of high-performance liquid chromatography. Protein binding was determined by use of an ultrafiltration device. RESULTS: Plasma data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean +/- SD values for half-life, volume of distribution, and clearance after IV administration for plasma samples were 0.67 +/- 0.07 hours, 0.372 +/- 0.053 L/kg, and 6.53 +/- 1.51 mL/min/kg, respectively, and half-life for tissue fluid samples was 1.15 +/- 0.57 hours. Half-life after SC administration was 0.98 +/- 0.21 and 1.31 +/- 0.54 hours for plasma and tissue fluid, respectively. Protein binding was 11.87%, and bioavailability after SC administration was 84%. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of our data revealed that tissue fluid and plasma (unbound fraction) concentrations were similar. Because of the kinetic similarity of meropenem in the extravascular and vascular spaces, tissue fluid concentrations can be predicted from plasma concentrations. We concluded that a dosage of 8 mg/kg, SC, every 12 hours would achieve adequate tissue fluid and urine concentrations for susceptible bacteria with a minimum inhibitory concentration of 0.12 microg/mL.     

Pharmacokinetic properties of theophylline given intravenously and orally to ruminating calves

The disposition of theophylline in healthy ruminating calves was best described by a first-order 2-compartment open pharmacokinetic model. The drug had a mean elimination half-life of 6.4 hours and a mean distribution half-life of 22 minutes. Total body clearance averaged 91 ml/kg/h. The mean values for the pharmacokinetic volume of the central compartment, pharmacokinetic volume of distribution during the terminal phase, and volume of distribution at steady state were 0.502, 0.870, and 0.815 L/kg, respectively. Theophylline was readily absorbed after oral administration to the ruminating calf, with a mean fraction of 0.93 absorbed. The plasma concentrations after oral dosing peaked in approximately 5 to 6 hours, with a mean absorption half-life of 3.7 hours. A flip-flop model (rate constant of input is much smaller than the rate constant of output) of drug absorption was not found because the elimination process roughly paralleled that of the study concerning IV administration. In a multiple-dose trial that used a dosage regimen based on single-dose pharmacokinetic values, clinically normal calves responded as predicted. However, diseased calves had higher than expected plasma concentrations after being given multiple oral doses of theophylline at 28 mg/kg once daily. Overt signs of toxicosis were not seen, but this aspect of the drug was not formally investigated. Theophylline can be used as an ancillary therapeutic agent to treat bovine respiratory disease, but not without risk. The suggested oral dose of theophylline at 28 mg/kg of body weight once daily should be tailored to each case.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic disposition of theophylline in horses after intravenous administration

The pharmacokinetics of theophylline were determined in 6 healthy horses after a single IV administration of 12 mg of aminophylline/kg of body weight (equivalent to 9.44 mg of theophylline/kg). Serum theophylline was measured after the IV dose at 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 15 hours. Serum concentration plotted against time on semilogarithmic coordinates, indicated that theophylline in 5 horses was best described by a 2-compartment open model and in 1 horse by a 1-compartment open model. The following mean pharmacokinetic values were determined; elimination half-life = 11.9 hours, distribution half-life = 0.495 hours, apparent specific volume of distribution = 0.885 +/- 0.075 L/kg, apparent specific volume of central compartment = 0.080 L/kg, and clearance = 51.7 +/- 11.2 ml/kg/hr. Three horses with reversible chronic obstructive pulmonary disease were serially given 1, 3, 6, 9, 12, and 15 mg of aminophylline/kg in single IV doses (equivalent to 0.8, 2.4, 4.7, 7.1, 9.44, and 11.8 mg of theophylline/kg, respectively). The horses were exposed to a dusty barn until they developed clinical signs of respiratory distress and were then given the aminophylline. Effects of increasing doses on different days were correlated with clinical signs, blood pH, and blood gases. The 3 horses had a decrease in the severity of clinical signs after the 9, 12, or 15 mg doses of aminophylline/kg. The horses at 0.5 hour after dosing had a significant decrease in PaCO2 (43.6 +/- 5.5 to 39.4 +/- 6.7 mm of Hg, P less than 0.001) and a significant increase in blood pH (7.38 +/- 0.017 to 7.41 +/- 0.023, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic properties of enrofloxacin in rabbits.

The pharmacokinetic properties of the fluoroquinolone antimicrobial enrofloxacin were studied in New Zealand White rabbits. Four rabbits were each given enrofloxacin as a single 5 mg/kg of body weight dosage by IV, SC, and oral routes over 4 weeks. Serum antimicrobial concentrations were determined for 24 hours after dosing. Compartmental modeling of the IV administration indicated that a 2-compartment open model best described the disposition of enrofloxacin in rabbits. Serum enrofloxacin concentrations after SC and oral dosing were best described by a 1- and 2-compartment model, respectively. Overall elimination half-lives for IV, SC, and oral routes of administration were 2.5, 1.71, and 2.41 hours, respectively. The half-life of absorption for oral dosing was 26 times the half-life of absorption after SC dosing (7.73 hours vs 0.3 hour). The observed time to maximal serum concentration was 0.9 hour after SC dosing and 2.3 hours after oral administration. The observed serum concentrations at these times were 2.07 and 0.452 micrograms/ml, respectively. Mean residence times were 1.55 hours for IV injections, 1.46 hours for SC dosing, and 8.46 hours for oral administration. Enrofloxacin was widely distributed in the rabbit as suggested by the volume of distribution value of 2.12 L/kg calculated from the IV study. The volume of distribution at steady-state was estimated at 0.93 L/kg. Compared with IV administration, bioavailability was 77% after SC dosing and 61% for gastrointestinal absorption. Estimates of predicted average steady-state serum concentrations were 0.359, 0.254, and 0.226 micrograms/ml for IV, SC, and oral administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of clomipramine in dogs following single-dose intravenous and oral administration

OBJECTIVE: To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose. ANIMALS: 6 male and 6 female Beagles. PROCEDURES: Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method. RESULTS: Time to peak plasma concentrations of clomipramine and desmethylclomipramine following oral administration was 1.2 hours. For clomipramine, after IV administration, elimination half-life was 5 hours, mean residence time was 3 hours, and plasma clearance was 1.4 L/h/kg. Values for mean residence time and terminal half-life following oral administration were similar to values obtained following IV administration, and systemic bioavailability was approximately 20% for clomipramine and 140% for desmethylclomipramine, indicating fast absorption of clomipramine from the gastrointestinal tract and extensive first-pass metabolism. Administration of clomipramine with food did not alter the area under the concentration versus time curve for desmethylclomipramine but resulted in a 25% increase for clomipramine. Clomipramine and desmethylclomipramine were extensively bound (> 96%) to serum proteins. There were no significant differences in area under the concentration versus time curve between male and female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that there should not be any clinically important differences in efficacy regardless of whether clomipramine is administered with or without food.     

Pharmacokinetics of ticarcillin in the dog

Five healthy adult dogs were given a single IV dose (40 mg/kg of body weight) of ticarcillin disodium. Serum concentrations were measured serially over a period of 12 hours. Five days later, the drug was administered IM to the dogs at the same dose rate, and serum concentrations were measured serially for 12 hours. The mean peak serum concentration after IM administration was 120.5 micrograms/ml at 1.5 hours. Pharmacokinetic values following IV administration were (i) elimination rate constant = 0.8/hour-1, (ii) half-life = 0.8 hour, (iii) serum clearance = 292 ml/hr/kg, and (iv) apparent volume of distribution = 347 ml/kg. Estimated values after IM administration were (i) elimination rate constant = 0.6/hour, (ii) half-life = 1.1 hours, (iii) serum clearance = 218 ml/hr/kg, and (iv) apparent volume of distribution = 345 ml/kg; only the elimination rate constants were significantly different between the 2 routes of administration.     

Pharmacokinetics of metronidazole given to horses by intravenous and oral routes

Serum and peritoneal fluid concentrations of metronidazole were determined in 6 healthy adult horses given the drug (25 mg/kg) by IV or oral routes. The disposition of metronidazole in horses given the drug by the IV route conformed to a 2-compartment model with a distribution half-life of 0.16 hours, an elimination half-life of 2.9 hours, and a body clearance of 0.40 +/- 0.05 L/kg/hr. The oral absorption half-life was 0.40 hours, and the bioavailability, 85.0 +/- 18.6%. Peritoneal fluid concentrations were approximately equal to serum concentrations at all times, regardless of the route of administration. On the basis of reported minimal inhibitory concentrations for anaerobic bacteria, a dosage of 15 to 25 mg/kg given orally 4 times daily was recommended.     

Pharmacokinetics of norfloxacin in dogs after single intravenous and single and multiple oral administrations of the drug

Norfloxacin was given to 6 healthy dogs at a dosage of 5 mg/kg of body weight IV and orally in a complete crossover study, and orally at dosages of 5, 10, and 20 mg/kg to 6 healthy dogs in a 3-way crossover study. For 24 hours, serum concentration was monitored serially after each administration. Another 6 dogs were given 5 mg of norfloxacin/kg orally every 12 hours for 14 days, and serum concentration was determined serially for 12 hours after the first and last administration of the drug. Complete blood count and serum biochemical analysis were performed before and after 14 days of oral norfloxacin administration, and clinical signs of drug toxicosis were monitored twice daily during norfloxacin administration. Urine concentration of norfloxacin was determined periodically during serum acquisition periods. Norfloxacin concentration was determined, using high-performance liquid chromatography with a limit of detection of 25 ng of norfloxacin/ml of serum or urine. Serum norfloxacin pharmacokinetic values after single IV dosing in dogs were best modeled, using a 2-compartment open model, with distribution and elimination half-lives of 0.467 and 3.56 hours (harmonic means), respectively. Area-derived volume of distribution (Vd area) was 1.77 +/- 0.69 L/kg (arithmetic mean +/- SD), and serum clearance (Cls) was 0.332 +/- 0.115 L/h/kg. Mean residence time was 4.32 +/- 0.98 hour. Comparison of the area under the curve (AUC; derived, using model-independent calculations) after iv administration (5 mg/kg) with AUC after oral administration (5 mg/kg) in the same dogs indicated bioavailability of 35.0 +/- 46.1%, with a mean residence time after oral administration of 5.71 +/-2.24 hours. Urine concentration was 33.8 +/- 15.3 micrograms/ml at 4 hours after a single dose of 5 mg/kg given orally, whereas concentration after 20 mg/kg was given orally was 56.8 +/- 18.0 micrograms/ml at 6 hours after dosing. Twelve hours after drug administration, urine concentration was 47.4 +/- 20.6 micrograms/ml after the 5-mg/kg dose and 80.6 +/- 37.7 micrograms/ml after the 20/mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thiacetarsamide in dogs: disposition kinetics and correlations with selected indocyanine green kinetic values

The pharmacokinetic values of thiacetarsamide (2.2 mg/kg) were determined in 6 healthy dogs after IV injection. A semilogarithmic plot of serum concentration vs time indicated that the 2-compartment open model best described thiacetarsamide disposition. A least-squares log linear regression microcomputer program was used to calculate the pharmacokinetic values. The mean elimination-phase half-life and clearance rate were 43 minutes and 200 ml/kg/min, respectively. Wide ranges in values were seen for the half-life (20.5 to 83.4 minutes) and the clearance rate (80.0 to 350.0 ml/kg/min). Before thiacetarsamide was given to the dogs, indocyanine green (ICG), an anionic dye that is eliminated almost entirely by hepatobiliary excretion, was administered IV at a dosage of 0.5 mg/kg of body weight. The half-life of ICG was 7.4 minutes, and the clearance rate was 8.43 ml/kg/min. There was a significant (P less than 0.01) correlation between the half-lives of thiacetarsamide and ICG, but not between the clearance rates. The variations in ICG half-lives and clearance rates were less than those seen for thiacetarsamide.     

Respiratory tract distribution and bioavailability of spiramycin in calves

Pharmacokinetic determinants of spiramycin and its distribution into the respiratory tract were studied in 2 groups of calves, 4 to 10 weeks old. Group-A calves (n = 4) were used to determine pharmacokinetic variables of spiramycin after IV (15 and 30 mg/kg of body weight) and oral administrations of the drug (30 mg/kg) and to measure distribution of spiramycin into nasal and bronchial secretions. Group-B calves (n = 4) were used to determine distribution of spiramycin into lung tissue and bronchial mucosa. Spiramycin disposition was best described by use of an open 3-compartment model. Mean (+/- SD) elimination half-life was 28.7 +/- 12.3 hours, and steady-state volume of distribution was 23.5 +/- 6.0 L/kg. Bio-availability after oral administration was 4 +/- 3%. High and persistent concentrations of spiramycin were achieved in the respiratory tract tissues and fluids. Tissue-to-plasma concentration ratio was 58 for lung tissue and 18 for bronchial mucosa at 3 hours after spiramycin administration and 137 and 49, respectively at 24 hours. Secretion-to-plasma concentration ratio was 4 for nasal secretions and 7 for bronchial secretions, and remained almost constant with time. Thus, spiramycin penetrates well into the respiratory tract, although the value in bronchial secretions is lower than that in lung tissues and bronchial mucosa. Calculations indicate that a loading dose of 45 mg/kg, administered IV, followed by a maintenance dose of 20 mg/kg, IV, once daily is required to maintain active concentrations of spiramycin against bovine pathogens in bronchial secretions.     

Pharmacokinetics and metabolic inertness of doxycycline in calves with mature or immature rumen function

The pharmacokinetic determinants of doxycycline were calculated after a single IV administration of the drug (20 mg/kg of body weight) in 5 Angus calves with mature rumen function and 4 Holstein calves with immature rumen function. Doxycycline disposition was best described by means of an open 2-compartment model. Median elimination half-life was 14.17 hours (Angus) and 9.84 hours (Holstein). Mean (+/- SEM) total body clearance was 1.07 (+/- 0.06) and 2.20 (+/- 0.21) ml/min/kg in Angus and Holstein calves, respectively. Mean extent of doxycycline binding to serum proteins was 92.3% (+/- 0.8%). The large steady-state volume of distribution (1.31 +/- 0.11 L/kg in Angus and 1.81 +/- 0.24 L/kg in Holstein calves), despite the small free fraction in serum, suggested a relatively unrestricted access of drug into the intracellular compartment and/or appreciable tissue binding. Results of mass spectrometric analysis of serum and urine from calves administered doxycycline IV revealed absence of biotransformation, because only parent drug could be detected. Thus, doxycycline may be a valuable antibiotic for use in food animals pending further studies on tissue residues, safety, and efficacy.