Comparison of two doses of aqueous bovine thyrotropin for thyroid function testing in dogs

Thyroid function was evaluated in 20 healthy dogs by thyrotropin (TSH) response testing. Two dose regimens were used: 5 IU of TSH given IV and 1 IU of TSH given IV. Blood samples were collected prior to and at 4 and 6 hours after TSH administration. Serum was obtained and analyzed for total 3,5,3'-tri-iodothyronine and thyroxine (T4) concentrations by radioimmunoassay. All dogs were classified as euthyroid on the basis of response to 5 IU of TSH at 4 and 6 hours. The 1-IU dose of TSH failed to induce adequate increase in T4 concentration in 7 dogs at 4 and 6 hours when the criteria for normal response were post-TSH serum concentration T4 greater than or equal to 3.0 micrograms/dl and serum T4 increase by greater than or equal to 100% over baseline serum T4 concentration. One IU of TSH induced increase in serum T4 concentration over baseline; however, the increase was significantly (P less than 0.05) less than that in response to a 5-IU dose at 6 hours after administration of TSH.     

Therapeutic serum concentrations of primidone and its metabolites, phenobarbital and phenylethylmalonamide in epileptic dogs

Fifteen dogs with idiopathic epilepsy were included in a 9-month clinical trial to determine the therapeutic serum concentrations of primidone and its active metabolites, phenobarbital and phenylethylmalonamide. Dogs with a seizure frequency greater than 1/mo or with a record of multiple seizures greater than 1/day were chosen for the study. Each dog was given primidone 3 times daily at dosages intended to maximize seizure control and to minimize undesired side effects. Maintenance period blood samples were taken from fasted dogs 7 hours after dosing in the 3rd, 5th, 7th, and 9th months of the trial to determine therapeutic serum concentrations of primidone and its metabolites. Two blood samples also were taken from all dogs 7 hours after dosing, during an enforced drowsy period, to establish upper limits of desirable serum concentrations of the drug. Seizure frequencies during the trial were controlled in 13 dogs, 7 of which had no seizures during the 9-month trial. The mean percentage reduction in seizure frequency from pretrial frequency was 85%. Two dogs appeared refractory to primidone therapy. Serum phenobarbital was the best metabolite of primidone to use to assess therapeutic serum concentrations. The therapeutic antiepileptic serum concentration of phenobarbital was found to be between 25 and 40 micrograms/ml of serum. Serum phenobarbital concentrations greater than 40 micrograms/ml resulted in side effects in most dogs.     

Serum digoxin concentrations in healthy dogs treated without a loading dose

Healthy dogs were treated once-a-day for 20 days, with a liquid oral dosage form of digoxin (0.022 mg/kg). Serum digoxin concentrations, measured by radio immunoassay technique, were in the therapeutic range 8 h after the second daily dose of digoxin had been administered. Of the ten dogs treated, four had digoxin serum concentrations above those accepted to be moderately toxic. Results of a blood urea nitrogen and a phenolsulfonphthalein test, determined at days 0, 5, 8, 12, 15 and 19 after the beginning of the investigation all were within normal limits. Serum osmolality, calcium, potassium, and sodium, determined daily, evidenced no significant difference from control values. Lengthening of the PR interval and a decrease in the heart rate were observed. Digitalization of dogs can be achieved without the use of a loading dose and within a much shorter time than was previously reported.     

Serum and tissue fluid norfloxacin concentrations after oral administration of the drug to healthy dogs

Norfloxacin, a 4-quinolone antibiotic, was administered orally to 4 healthy dogs at dosages of 11 and 22 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) norfloxacin concentrations were measured at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after the first and seventh dose of each dosing regimen. When administered at a dosage of 11 mg/kg, the mean peak serum concentration (Cmax) was 1.0 microgram/ml at 1 hour, the time of mean peak concentration (Tmax) after the first dose. After the seventh dose, the Cmax was 1.4 micrograms/ml at Tmax of 1.5 hours. The Tmax for the TCF concentration was 5 hours, with Cmax of 0.3 microgram/ml and 0.7 microgram/ml after the first and seventh dose, respectively. When administered at a dosage of 22 mg/kg, the serum Tmax was 2 hours after the first dose, with Cmax of 2.8 micrograms/ml. After the seventh dose, the serum Tmax was 1.5 hours, with Cmax of 2.8 micrograms/ml. The Tmax for the TCF concentration was 5 hours after the first and seventh doses, with Cmax of 1.2 micrograms/ml and 1.6 micrograms/ml, respectively. After the seventh dose, the serum elimination half-life was 6.3 hours for a dosage of 11 mg/kg and was 6.7 hours for a dosage of 22 mg/kg. For serum concentration, the area under the curve from 0 to 12 hours (AUC0----12) was 8.77 micrograms.h/ml and 18.27 micrograms.h/ml for dosages of 11 mg/kg and 22 mg/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum thyroid hormone concentrations and thyrotropin responsiveness in dogs with generalized dermatologic disease.

Fifty-eight dogs with generalized dermatologic disease that had not been given glucocorticoids systemically or topically within 6 weeks of entering the study were evaluated for thyroid function by use of the thyrotropin-response test. Dogs were classified as euthyroid or hypothyroid on the basis of test results and response to thyroid hormone replacement therapy. Baseline serum thyroxine (T4), free T4 (fT4), and triiodothyronine (T3) concentrations were evaluated in the 58 dogs. Serum T4, fT4, and T3 concentrations were evaluated in 200 healthy dogs to establish normal values. Hormone concentrations were considered low if they were less than the mean -2 SD of the values for control dogs. Specificity of T4 and fT4 concentrations was 100% in predicting hypothyroidism; none of the euthyroid dogs with generalized skin disease had baseline serum T4 or fT4 concentration in the low range. Sensitivity was better for fT4 (89%) than for T4 (44%) concentration. Significant difference was not observed in serum T4 and fT4 concentrations between euthyroid dogs with generalized skin disease and healthy control dogs without skin disease. Serum T3 concentration was not accurate in predicting thyroid function; most of the euthyroid and hypothyroid dogs with skin disease had serum T3 concentration within the normal range.     

Pharmacokinetic evaluation of enrofloxacin administered orally to healthy dogs.

Enrofloxacin was administered orally to 6 healthy dogs at dosages of approximately 2.75, 5.5, and 11 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosage regimens. Serum and tissue cage fluid (TCF) concentrations of enrofloxacin were measured after the first and seventh treatments. The mean peak serum concentration occurred between 1 and 2.5 hours after dosing. Peak serum concentrations increased with increases in dosage. For each dosage regimen, there was an accumulation of enrofloxacin between the first and seventh treatment, as demonstrated by a significant (P = 0.001) increase in peak serum concentrations. The serum elimination half-life increased from 3.39 hours for the 2.75 mg/kg dosage to 4.94 hours for the 11 mg/kg dosage. Enrofloxacin accumulated slowly into TCF, with peak concentrations being approximately 58% of those of serum. The time of peak TCF concentrations occurred between 3.8 hours and 5.9 hours after drug administration, depending on the dosage and whether it was after single or multiple administrations. Compared with serum concentrations (area under the curve TCF/area under the curve serum), the percentage of enrofloxacin penetration into TCF was 85% at a dosage of 2.75 mg/kg, 83% at a dosage of 5.5 mg/kg, and 88% at a dosage of 11 mg/kg. All 3 dosage regimens of enrofloxacin induced continuous serum and TCF concentrations greater than the minimal concentration required to inhibit 90% (MIC90) of the aerobic and facultative anaerobic clinical isolates tested, except Pseudomonas aeruginosa.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of dose and concentration on D-xylose absorption in healthy,immature dogs

Nine combinations of dosages and concentrations of D-xylose were given orally to eight clinically normal, immature dogs. The concentrations and dosages of D-xylose consisted of 5%, 10%, and 20% at 250 mg/kg, 500 mg/kg, and 750 mg/kg. Serum samples were collected at 0, 30, 60, 90, 120, and 180 minutes. Serum xylose was quantitated using the phloroglucinol microassay technique. A peak in serum xylose concentration was seen for each treatment combination at 60 or 90 minutes after dosing. The dosage effect was important in influencing serum xylose values (P < 0.0001). As the test solution dosages increased from 250 mg/kg to 500 mg/kg and 750 mg/kg, serum xylose values (when dosage was analyzed over the length of the entire test) rose linearly (R(2) = 0.98). The treatment combinations of 5% and 20% xylose solutions dosed at 750 mg/kg produced the highest serum xylose values at the 60- and 90-minute peak intervals. The independent effect of concentration was significant (p < 0.001) but was overridden by the stronger dosage effect. Serum xylose concentrations varied little statistically (p > 0.05) when the 5%, 10%, and 20% solutions were compared at a specific dosage.     

Effects of short-term trimethoprim-sulfamethoxazole administration on thyroid function in dogs

OBJECTIVE: To determine how rapidly trimethoprim-sulfamethoxazole affects serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in euthyroid dogs and how quickly hormone concentrations return to reference values following discontinuation of administration. DESIGN: Prospective study. ANIMALS: 7 healthy euthyroid dogs. PROCEDURE: Dogs were given trimethoprim-sulfamethoxazole (26.5 to 31.3 mg/kg [12 to 14.2 mg/lb], PO, q 12 h) for a maximum of 6 weeks. A CBC and Schirmer tear test were performed and serum total T4 and TSH concentrations were measured weekly. Administration of trimethoprim-sulfamethoxazole was discontinued if total T4 concentration was less than the lower reference limit and TSH concentration was greater than the upper reference limit or if persistent neutropenia developed. RESULTS: Six dogs had total T4 concentrations less than the lower reference limit within 3 weeks; T4 concentration was decreased after 1 week in 3 of these 6 dogs. In these 6 dogs, TSH concentration was greater than the upper reference limit within 4 weeks. In 1 dog, T4 and TSH concentrations were not affected, despite administration of trimethoprim-sulfamethoxazole for 6 weeks. Neutropenia developed in 4 dogs. In 1 dog, the neutropenia resolved while trimethoprim-sulfamethoxazole was still being administered. In the other 3, neutrophil counts returned to reference values 1 week after drug administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of trimethoprim-sulfamethoxazole at a dosage of 26.5 to 31.3 mg/kg, PO, every 12 hours can substantially alter serum total T4 and TSH concentrations and neutrophil counts in dogs within as short a time as a few weeks.     

Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) – a software program designed to determine intravenous drug dosage regimens for veterinary applications

Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) is a soft-ware program used to design individualized intravenous dosage regimens, determine concentration-time profiles, predict serum concentrations at a specific time after intravenous dosing and predict the time after the last dose to achieve a specified concentration of drug. The reference pharmacokinetic parameters may be based on an individual animal's pharmacokinetic disposition of drug or on FARAD (Food Animal Residue Avoidance Databank) mean population kinetic parameters. An individual animal's kinetic parameters may be input for predetermined analysis or the program can calculate these values by input of raw serum concentration-time data. The program allows the user to specify certain parameters of the dosage regimen, then calculates the other parameters (given desired maximum and minimum serum concentrations, dose and interval are calculated; given desired maximum serum concentration and interval, dose is calculated, etc.). Given the kinetic parameters, the dose and dosing interval, the program calculates and plots the serum concentration-time profile of the drug for that animal. The time and the number of doses to reach steady state can be calculated as well as the determination of loading dose. The percentage of the time of a dosing interval at steady state that the serum concentration is above a specific minimum inhibitory concentration (MIC) allows evaluation of efficacy of an antimicrobial regimen. Similarly, the time to reach a specific concentration (e.g. residue tolerance) or the MIC of a drug can be calculated. Legal tissue tolerances can be accessed from FARAD to aid in predicting for what period of time illegal residues will remain in the animal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum salicylate concentrations and endoscopic evaluation of the gastric mucosa in dogs after oral administration of aspirin-containing products

The serum salicylate concentration produced by oral administration of plain aspirin and several aspirin-containing products given at 8-hour intervals for 7 treatments was measured in 36 laboratory-conditioned adult dogs. The dogs were randomly allotted to 6 groups of 6 dogs each: group 1 was given plain aspirin at a dosage of 25 mg/kg of body weight: group 2 was given plain aspirin at a dosage of 10 mg/kg; group 3 was given buffered aspirin at a dosage of 25 mg/kg; group 4 was given enteric-coated aspirin at a dosage of 25 mg/kg; group 5 was given buffered aspirin at a dosage of 25 mg/kg; and, group 6 was given a placebo. Serum salicylate concentration was measured at 2-hour intervals for the first 8 hours, and then at 8-hour intervals for the next 40 hours. Following the last dosing, serum salicylate concentration was measured at 2-hour intervals until 56 hours; the final 2 samples were measured at 64 and 72 hours. The effect of aspirin on the gastric mucosa was studied in 12 dogs, 3 each randomly selected from groups 1, 3, 4, and 5. The gastric mucosa of each dog was examined with a fiberoptic gastroscope 3 days before the beginning of treatment; lesions were not seen. The drugs were administered as described and the gastric mucosa of each dog was reexamined at 72 hours. Administration of the aspirin-containing products at 8-hour intervals resulted in sustained therapeutic serum salicylate concentrations (greater than 5 mg/dl) in all dogs, except those of group 2. The greatest fluctuation in serum salicylate concentration was found in dogs of group 4. Gastric lesions were seen only in the 3 dogs of group 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serial thyroid hormone concentrations in healthy euthyroid dogs, dogs with hypothyroidism, and euthyroid dogs with atopic dermatitis.

Serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) concentrations were determined every 3 h for 12 h beginning at 8 a.m. in 20 healthy euthyroid dogs, 19 dogs with hypothyroidism, and 18 euthyroid dogs with atopic dermatitis. Status of thyroid function was based on history, physical findings, results of thyrotropin response testing, and requirement for thyroid hormone replacement therapy. Mean serum T4 and T3 concentrations did not vary significantly between blood samplings within each of the three groups of dogs. Between groups of dogs, mean serum T4 concentration was significantly (P less than 0.05) higher at each blood sampling time in healthy euthyroid dogs and euthyroid dogs with atopic dermatitis when compared to dogs with hypothyroidism. There was no significant difference in mean serum T4 concentration at any blood sampling time between healthy euthyroid dogs and euthyroid dogs with atopic dermatitis or in mean serum T3 concentrations at any blood sampling time between any of the three groups of dogs. Random fluctuation in serum T4 and T3 concentrations was found in dogs in all three groups. Random fluctuations were more common with serum T3 versus T4 concentrations. Consequently, sensitivity (0.88 versus 0.52), specificity (0.73 versus 0.45), predictive value for a positive test (0.75 versus 0.32), predictive value for a negative test (0.87 versus 0.65), and accuracy (0.80 versus 0.47) were better for serum T4 concentration than serum T3 concentration, respectively, when all blood samples were analysed. Measurement of serum T4 concentration was more accurate than serum T3 concentration in assessing the status of thyroid gland function.     

Effect of oral administration of prednisolone on thyroid function in dogs

To determine the effect of oral administration of prednisolone on thyroid function, 12 healthy Beagles were given 1.1 mg of prednisolone/kg of body weight every 12 hours for 22 days after 8 days of diagnostic testing of the dogs before treatment with prednisolone. Thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) response tests were performed before treatment (days 1 and 8 of the study) and during treatment (days 21 and 28 of the study). Blood samples were collected daily at 8 AM and 2 and 8 PM to rule out normal daily hormone fluctuations as the cause of a potential decrease in serum triiodothyronine (T3), thyroxine (T4), and free T4 (fT4) concentrations. Serum T3, T4, and fT4 concentrations before treatment and 1 day and 21 days after the first prednisolone dose were compared by analyses of variance. Post-TSH and -TRH serum T3 and T4 concentrations before and during treatment were compared, using the Student t test for paired data. Oral administration of prednisolone significantly (P less than 0.005) decreased serum T3, T4, and fT4 concentrations in the 8 AM and 2 and 8 PM samples obtained 1 day and 21 days after the first prednisolone dose. Serum T4 and fT4 concentrations in 8 AM and 2 PM samples were significantly (P less than 0.05) lower 21 days after the first prednisolone dose than they were at 1 day after the first dose. Before treatment, serum T4 concentration in the 2 PM samples was significantly (P less than 0.05) higher than serum T4 concentration in 8 AM and 8 PM samples.(ABSTRACT TRUNCATED AT 250 WORDS)     

Zonisamide therapy for refractory idiopathic epilepsy in dogs

Twelve dogs with poorly controlled idiopathic epilepsy were entered into a prospective, open-label, noncomparative study. Oral zonisamide was administered as an additional therapy at a dosage adequate to achieve serum drug concentrations of 10 to 40 microg/mL. Seizure frequency before and after initiation of zonisamide therapy was recorded. A dosing interval of q 12 hours was sufficient to maintain serum zonisamide concentrations within the therapeutic range. The mean dosage of zonisamide required was 8.9 mg/kg q 12 hours. Seven (58%) dogs responded favorably, experiencing a mean reduction in seizures of 81.3%. Five dogs had an increase in seizure frequency. Mild side effects (e.g., transient sedation, ataxia, vomiting) occurred in six dogs.     

Kinetic study of serum gentamicin concentrations in baboons after single-dose administration

This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered IM to baboons. Serum concentrations greater than or equal to 12 micrograms/ml are generally agreed to cause toxicosis in human beings. On the basis of preliminary test results suggesting that the manufacturer's recommended dosage for dogs of 4.4 mg/kg of body weight caused potentially toxic serum concentrations, a dosage of 3 mg/kg was chosen to conduct a single-dose kinetic study in 6 baboons. Using a single-compartment model, the gentamicin serum half-life for IM administration of 3 mg of gentamicin/kg was 1.58 hours, and serum concentrations remained below the potentially toxic concentrations reported for human beings. We suggest that a dosage of 3 mg/kg is safer than a dosage of 4.4 mg/kg administered IM to baboons. Minimal inhibitory concentrations for 2 Pseudomonas aeruginosa isolates were less than or equal to 1 micrograms/ml. On the basis of our measured elimination half-life of 1.58 hours, it is reasonable to suppose that dosing q24 h will be inadequate to maintain therapeutic serum concentrations. We calculate that serum concentrations will remain at or above our measured minimal inhibitory concentration for P aeruginosa (1 micrograms/ml) for 100% of the treatment time if the animal is dosed q 6h, 78% for dosing q 8h, and 52% for dosing q 12h. Therefore, we suggest 3 mg/kg, q 8h or q 6h as appropriate dosing schedules for the use of gentamicin sulfate administered IM to baboons.     

Serum and tissue cage fluid concentrations of ciprofloxacin after oral administration of the drug to healthy dogs

Ciprofloxacin, a fluoroquinolone antimicrobial agent, was administered orally to 4 healthy dogs at dosage of approximately 11 and 23 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) concentrations of ciprofloxacin were measured after the first and seventh dose of each dosing regimen. The peak concentration was greatest in the serum after multiple doses of 23 mg/kg (mean +/- SEM; 5.68 +/- 0.54 micrograms/ml) and least in the TCF after a single dose of 11 mg/kg (0.43 +/- 0.54 micrograms/ml). The time to peak concentration was not influenced by multiple dosing or drug dose, but was longer for TCF (6.41 +/- 0.52 hour) than for serum (1.53 +/- 0.52 hour). Accumulation of ciprofloxacin was reflected by the area under the concentration curve from 0 to 12 hours after administration (AUC0----12). The AUC0----12 was greatest in the serum after multiple doses of 23 mg/kg (31.95 +/- 1.90 micrograms.h/ml) and least in the TCF after a single dose of 11 mg/kg (3.87 +/- 1.90 micrograms.h/ml). The elimination half-life was not influenced by multiple dosing or dose concentration, but was greater for TCF (14.59 +/- 1.91 hours) than for serum (5.14 +/- 1.91 hours). The percentage of TCF penetration (AUCTCF/AUCserum) was greater after multiple doses (95.76 +/- 6.79%) than after a single dose (55.55 +/- 6.79%) and was not different between doses of 11 and 23 mg/kg. Both dosing regimens of ciprofloxacin resulted in continuous serum and TCF concentrations greater than 90% of the minimal inhibitory concentration for the aerobic and facultative anaerobic clinical isolates tested, including Pseudomonas aeruginosa.     

Acute cardiovascular effects of diltiazem in anesthetized dogs with induced atrial fibrillation

Atrial fibrillation (AF) is one of the most important arrhythmias of dogs. In a previous study, we determined the dosage of intravenously administered diltiazem necessary to reduce ventricular response (VR), cardiac output (CO), and mean systemic arterial pressure (P(Ao)) to values similar to those observed during sinus rhythm (SR) before induction of AF. The present study was conducted to establish an acute, effective dosage of diltiazem given PO. AF was produced by rapid atrial pacing in healthy, anesthetized Beagle Hounds. Dogs were instrumented to record hemodynamic and electrophysiological parameters. Four dogs were given 2.5 mg/kg diltiazem, and another 4 dogs were given 5 mg/kg diltiazem by stomach tube, whereas 4 other dogs received vehicle in equivalent volumes. Plasma concentrations of diltiazem were measured at various intervals after dosing. A dosage of 5 mg/kg diltiazem produced plasma concentrations of 32-100 ng/mL 3 hours after administration, concentrations within the published effective range for dogs with naturally occurring AF. Between 2 and 3 hours after this dosage, the rate pressure product (RPP) and an index of left ventricular efficiency returned to values similar to those observed during SR. Thus, we believe that diltiazem at anorally administered dosages of 5 mg/kg should be considered to produce therapeutic blood concentrations and favorable hemodynamic effects in dogs with naturally occurring AF. These data must be extrapolated with caution to dogs with long-standing AF produced by natural causes.     

Effects of propranolol on thyroid function in the dog

The effect of propranolol on thyroid function was evaluated in 6 mature euthyroid Beagles. Propranolol was administered orally in doses of 20 mg given 3 times daily for 2 weeks and then increased to 40 mg given 3 times daily for an additional 2 weeks. Six age- and sex-matched, euthyroid Beagles served as controls. Serum base-line concentrations of tetraiodothyronine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) were measured before propranolol administration and at weekly intervals thereafter. Thyroid response to 5 IU of aqueous thyroid stimulating hormone administered IV was monitored before propranolol administration and at the 2- and 4-week treatment intervals. The T4, T3, and rT3 concentrations were measured by radioimmunoassay. There were no significant differences in base-line or postthyroid stimulating hormone serum concentrations of T4, T3, or rT3 in any individual or between the treatment or control groups at any treatment interval (P greater than 0.05). Seemingly, the therapeutic use of propranolol in euthyroid dogs should not alter thyroid hormone metabolism.     

Pharmacokinetic adjustment of gentamicin dosing in horses with sepsis

Serum gentamicin concentrations were measured and pharmacokinetic values were calculated for 12 equine patients receiving parenteral gentamicin therapy. Horses were selected for monitoring of gentamicin pharmacokinetics if they met several criteria of high risk for gentamicin-induced toxicosis. Two blood samples were obtained, one immediately before gentamicin dosing and one at 1 hour after dosing. Gentamicin serum concentrations were analyzed and dosage adjustments were made on the basis of calculated one-compartment pharmacokinetic values. Nine of the 12 horses required dosage adjustment to optimize therapeutic concentrations. Even for horses for which there was no evidence of decreased renal function, variation in the disposition of gentamicin was substantial. Because of the larger volume of distribution in foals, an initial dosage of 3 mg/kg every 12 hours was found to best approximate target concentrations. Therefore, published standard dosages were a poor means of achieving desired peak and trough concentrations in many animals. Seemingly, for optimal treatment of horses with sepsis, gentamicin dosage adjustments based on the patient's pharmacokinetic values is required.     

Pharmacokinetic evaluation of ceftiofur in serum, tissue chamber fluid and bronchial secretions from healthy beef-bred calves.

Ceftiofur is a new broad spectrum cephalosporin marketed for the treatment of acute bovine respiratory disease. In this investigation ceftiofur was administered by intramuscular injection, at 24 h intervals, to healthy beef-bred calves for four days at dosages of 2.2 and 4.4 mg/kg of body weight, with 4 wk intervals between dosing regimens. Serum, tissue chamber fluid (TCF), and bronchial secretion (BS) concentrations of ceftiofur were measured by microbiological assay after the first and fourth dose of each dosing regimen. Peak serum concentrations (Cmax) of 8.8 micrograms/mL and 17.3 micrograms/mL were obtained approximately 2 h (Tmax), the time of mean peak concentration) after single injections of 2.2 mg/kg and 4.4 mg/kg, respectively. The Cmax was increased approximately twofold following multiple doses of 2.2 mg/kg (Cmax = 13.1 micrograms/mL) and 4.4 mg/kg (Cmax = 24.1 micrograms/mL). Ceftiofur accumulated slowly into TCF and peak concentrations were found to be approximately 14% of those observed in serum after the first dose and approximately 24% after multiple dosing. Concentrations of ceftiofur in BS were obtained rapidly with peak concentrations reaching 45% of the serum Cmax after the first dose. After multiple dosing the Cmax for BS was approximately 25% of the serum Cmax. This study found that both the 2.2 mg/kg and 4.4 mg/kg dosing regimens resulted in continuous serum, TCF and BS concentrations of ceftiofur that exceeded the minimal concentration required to inhibit the bacteria most frequently isolated from calves with acute bovine respiratory disease.     

Effect of timing of blood collection on serum phenobarbital concentrations in dogs with epilepsy

OBJECTIVE: To determine whether there are therapeutically relevant changes in serum phenobarbital concentrations throughout a daily dosing interval in epileptic dogs receiving phenobarbital for > or = 3 weeks. DESIGN: Prospective study. ANIMALS: 33 epileptic dogs receiving phenobarbital. PROCEDURE: Serum phenobarbital concentrations were measured at 0 hour (trough), 3 hours, and 6 hours after oral administration of phenobarbital in epileptic dogs that had received phenobarbital twice daily for a minimum of 3 weeks. For each dog, trough, 3-hour, and 6-hour serum phenobarbital concentrations were evaluated to determine whether they were within the same therapeutic category (lower, middle, or upper end of the therapeutic range of 15 to 45 micrograms/ml), or whether there was a > 30% change in serum concentrations throughout the day. RESULTS: Ninety-one percent (30/33) of dogs had trough, 3-hour, and 6-hour serum phenobarbital concentrations in the same therapeutic category. Only 9% (3/33) of dogs had trough, 3-hour, and 6-hour serum concentrations in different therapeutic categories with a > 30% change in concentrations throughout the day. Significant differences were not detected among mean serum phenobarbital concentrations when comparing the trough, 3-hour, and 6-hour samples for all dogs. CONCLUSIONS AND CLINICAL RELEVANCE: There is no therapeutically relevant change in serum phenobarbital concentrations throughout a daily dosing interval in most epileptic dogs. Therefore, timing is not important when collecting blood samples to measure serum phenobarbital concentrations in most epileptic dogs treated long-term with phenobarbital.