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T Whittem

Publications and source records attributed to T Whittem.

At least 19 recordsLinked to original sources
PubMed2000

The pharmacokinetics and effects of intravenously administered carprofen and salicylate on gastrointestinal mucosa and selected biochemical measurements in healthy cats.

The pharmacokinetics of carprofen, a propionic acid-derived nonsteroidal anti-inflammatory (NSAID), and its effect on gastrointestinal mucosa, complete blood counts (CBC) and biochemical indicators of liver and renal function were investigated in healthy cats using a randomized crossover design. A single dose of 4 mg/kg of carprofen (Zenecarp(R) Injection), normal saline, or 20 mg/kg of DL-lysine acetyl salicylate (Vetalgine(R)) was given intravenously (i.v.) to each of five cats with a washout period of 2 weeks between treatments. Endoscopy of the stomach and duodenum 8 h postinjection revealed one acetyl salicylate-(aspirin)-treated cat with minor pinpoint erosions. None of the other cats in the three treatment groups had evidence of bleeding or ulceration. Serum biochemistry measurements of blood urea nitrogen (BUN), alanine transferase (ALT) and alkaline phosphatase (ALP) and complete blood counts (CBC) were not significantly altered from pretreatment values by the single dose of salicylate or carprofen (P < 0.05). Early and extended sample time points suggest that the pharmacokinetics of carprofen in the cat fit a 2-compartment model, with a long elimination half-life (t1/2) of 20.1 +/- 16.6 h, an area under the plasma concentration-time curve (AUC) of 637 (+/- 237) microgram.mL/h and a volume of distribution (Vdss) of 0.14 +/- 0.05 L/kg. Intravenously administered aspirin fit a 2-compartment model and had a long elimination half-life (t1/2) of 22.2 +/- 3.1 h, an AUC of 3824.2 +/- 506.7 microgram.mL/h and a volume of distribution (Vdss) of 0.17 +/- 0. 01 L/kg.

Alanine Transaminase↗
PubMed1999

Formulary of common equine drugs.

This article presents in easily accessible form a collection of drug names and dose rates for the drugs recommended or referred to by the authors of the individual articles in this issue. Although the formulary provides recommendations for drug use, the reader is cautioned that the responsibility for the choice of agent, formulation, dose, and dose interval lies with the clinician. The author also addresses regulations that govern the use of drugs in competition horses.

Animals↗
PubMed1999

Pharmacokinetics and milk discard times of pirlimycin after intramammary infusion: a population approach.

A population pharmacokinetic approach was used to analyse milk concentration data to determine whether milk discard times and the clearance of intramammary infusions of pirlimycin could be adequately predicted by readily available demographic variables. Milk samples were collected at 12 hourly milking intervals after dosing with pirlimycin during product development from both normal cows (primary data) and cows with naturally occurring mastitis (validation data) and pirlimycin concentration was determined by microbial inhibition assay. The data were analysed by the conditional estimation/ maximum likelihood population approach within the computer program PPharm and fitted a two compartment open model. Bayesian estimates of individual parameters allowed solutions for each cow, predicting the time after last dosing by which milk concentration reached the target safe concentration. From this population of times, the 95% confidence interval of the 99th percentile was defined as the milk discard time. After elimination of one very low producing outlier, the calculated discard time agreed with the label recommendation of 36 h (3 milkings, USA) after the last dose. Milk pirlimycin clearance was strongly and positively correlated to the logarithm of the kilograms of milk produced in 24 h at time of dosing (r2=0.939). Agreement was strong at most time points between predicted and measured pirlimycin concentrations in milk from cows with mastitis. This alternative method for determining milk discard times was compared to existing recommendations.

Animals↗
PubMed1999

Methicillin resistance among staphylococci isolated from dogs.

OBJECTIVE: To determine whether methicillin-resistant staphylococci from dogs expressed the mecA gene and to determine what proportion of canine staphylococcal isolates positive for the mecA gene were resistant to oxacillin and other antibiotics. SAMPLE POPULATION: 25 methicillin-resistant (10 coagulase-positive and 15 coagulase-negative) and 15 methicillin-susceptible (8 coagulase-positive and 7 coagulase-negative) staphylococci isolated from dogs. PROCEDURE: All strains were tested for methicillin resistance by use of oxacillin agar screening and identified by use of standard techniques. Minimum inhibitory concentrations of 16 antibiotics were determined for all 40 isolates. A polymerase chain reaction method targeting a 533-basepair fragment of the mecA gene was used to detect mecA gene expression. RESULTS: 23 of the 25 methicillin-resistant isolates and none of the methicillin-susceptible isolates possessed the mecA gene. For 10 of 16 antibiotics, the proportion of mecA-positive isolates that were resistant or of intermediate susceptibility was significantly higher than the proportion of mecA-negative isolates that were resistant or of intermediate susceptibility. Only 1 methicillin-resistant coagulase-positive isolate was identified as Staphylococcus intermedius; the other 9 were identified as S. aureus. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirm that staphylococci isolated from dogs may have methicillin resistance mediated by the mecA gene. Isolates positive for the mecA gene were more likely to be resistant to various antibiotics than were isolates negative for the mecA gene. Results suggest that in dogs, infections caused by staphylococci that have the mecA gene may be difficult to treat because of resistance to antibiotics.

Ampicillin Resistance↗
PubMed1998

Principles of antimicrobial therapy.

It has been 2500 years since the Chinese began applying moldy soybean curd to cure skin infections. Technology today has refined the benefits of antibiotic-forming molds and bacteria and has greatly increased the number of antimicrobial drugs available to combat infection. Understanding the principles fundamental to rational therapy with these drugs will ensure the best of possible outcomes.

Animals↗
PubMed1997

Dihydrostreptomycin or streptomycin in combination with penicillin G in dairy cattle therapeutics: a review and re-analysis of published data. Part 1: clinical pharmacology.

Combination formulations of penicillin G salts and dihydrostreptomycin were developed during the 1960s and are currently marketed in New Zealand for parenteral and intramammary use in dairy cattle. In this paper, the clinical indications and efficacy, pharmacokinetics and potential for antimicrobial synergy of penicillin and dihydrostreptomycin or streptomycin, when combined, are discussed.

Journal Article↗
PubMed1997

Dihydrostreptomycin or streptomycin in combination with penicillin G in dairy cattle therapeutics: a review and re-analysis of published data. Part 2: resistance and residues.

Combination formulations of penicillin G salts and dihydrostreptomycin were developed during the 1960s and are currently marketed in New Zealand for parenteral and intramammary use in dairy cattle. In this paper, the second part of a two paper series, the mechanisms by which bacteria develop resistance to each of these drugs independently is reviewed and the impact of this resistance on potential for synergy is discussed. Further, the considerable potential for tissue drug residues with dihydrostreptomycin or streptomycin from these formulations is examined by re-analysis of literature data, demonstrating an urgent need to reassess the place for aminoglycoside-containing formulations in dairy cattle therapeutics.

Journal Article↗
PubMed1997

Pharmacokinetics of propranolol in healthy cats during euthyroid and hyperthyroid states.

OBJECTIVE: To examine the pharmacokinetic profile of propranolol in cats before and during experimentally induced hyperthyroidism. ANIMALS: 8 conditioned, random-source, young adult, female cats. PROCEDURE: Propranolol was administered i.v. as a single bolus and 72 hours later by mouth. Thereafter, the cats were dosed for 5 weeks with L-thyroxine (50 micrograms/kg of body weight, s.c., once daily) to induce hyperthyroidism (serum thyroxine concentration, 217 +/- 17 nmol/L). Blood samples were obtained at appropriate intervals before and during hyperthyroidism and were analyzed for plasma propranolol concentration by use of high-performance liquid chromatography. RESULTS: In all cats, a two-compartment model best described the control and hyperthyroid intravenous data. The change in thyroid status from euthyroid to hyperthyroid caused a significant (P < 0.05), but small reduction in propranolol area under the curve (19,932 +/- 7,900 min.micrograms/L vs 15,911 +/- 1,400 min.micrograms/L) after i.v. administration. In contrast, after oral administration during the hyperthyroid state, a twofold increase (P < 0.05) in propranolol area under the curve (105,430 +/- 57,600 min.micrograms/L vs 226,811 +/- 112,000 min.micrograms/L) and peak serum propranolol concentration (651 +/- 247 micrograms/L vs 1191 +/- 590 micrograms/L) were attributed to significant (P < 0.05) increase in propranolol bioavailability caused by increased fractional absorption (57 +/- 28% vs 137 +/- 73%) and decreased total body clearance (58 +/- 27 ml/min/kg vs 30 +/- 19 ml/min/kg). Mean arrival time after oral dosing was significantly lengthened by hyperthyroidism (100 +/- 38 minutes vs 157 +/- 71 minutes). CLINICAL RELEVANCE: Hyperthyroidism-induced changes in propranolol pharmacokinetics may signal the need to reduce doses of propranolol when they are orally administered to hyperthyroid cats.

Administration, Oral↗
PubMed1996

Contrast between the pharmacokinetics of two formulations of cephalexin after intramuscular administration in cattle.

Two commercial formulations of cephalexin were administered intramuscularly to five heifers and five bulls in a balanced crossover design. Statistically significant and clinically important differences were detected between the two formulations of cephalexin. These results suggest that 24 h dose intervals would be appropriate with only one of the formulations and that the recommended dose rates for each product may need to be reviewed.

Journal Article↗
PubMed1996

The pharmacokinetics of salicylate in dairy cattle are not altered by simultaneous intravenous ceftiofur sodium and DL-lysine-acetyl salicylate (aspirin).

This study evaluated potential alterations to the pharmacokinetics of salicylate by concurrently administered ceftiofur sodium. The trial design was a cross-over using 10 non-lactating, non-pregnant dairy cows. In the first period each cow received intravenously (i.v.) 26 mg/kg of DL-lysine acetyl salicylate (aspirin) followed immediately by 2 mg/kg ceftiofur sodium. In the second period each cow received 26 mg/kg of aspirin i.v. Plasma samples were harvested for determination of salicylate concentration by HPLC. The data best fitted a single compartment open model, using weighted non-linear regression. No alterations to the pharmacokinetic parameters of salicylate in cattle by concurrently administered ceftiofur sodium were detected (P < 0.05). Using 90% confidence intervals, and testing for changes of > 20%, control values, elimination half-life (t1/2), apparent volume of distribution (Vd), area under the plasma concentration versus time curve (AUC) and mean residence time (MRT) were not altered. For control animals the elimination rate constant (k(el)) and total body clearance (Cl) were 1.35 +/- 0.43 h-1 and 20.2 +/- 6.1 ml/h.kg respectively (mean +/- SD). Since ceftiofur sodium did not affect the pharmacokinetics of salicylate, dose regimens for aspirin in cattle need not be altered when ceftiofur sodium is administered concurrently.

Animals↗
PubMed1996

Pharmacokinetic interactions between repeated dose phenylbutazone and gentamicin in the horse.

This study examined the pharmacokinetics of steady-state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone concentration determination by high-performance liquid chromatography. All gentamicin data were best approximated by a two-compartment open model using sequential, weighted non-linear regression. Pharmacokinetic parameters were calculated using model-dependent formulae. Phenylbutazone data were analysed by non-compartmental methods. Phenylbutazone induced a 49% increase in the rate of gentamicin return to the central compartment from peripheral tissues (k21) (P < 0.05) and there was a trend to a 24% increase in k12 (P = 0.052). The gentamicin elimination half-life was decreased 23% and the Vd(urea) was reduced by 26%. No induction by gentamicin of changes in phenylbutazone pharmacokinetics were detected. In summary, phenylbutazone induced changes to the rate and extent of distribution and elimination of gentamicin. Therefore, care should be exercised in the use of aminoglycosides in equine patients concurrently maintained on phenylbutazone.

Animals↗
PubMed1996

Inflammatory mediators in equine synovial fluid.

Enzyme immunoassay for prostaglandin E2 (PGE2), and radioimmunoassays for prostaglandin F2 alpha (PGF2 alpha), 6-keto-PGF1 alpha, and leukotriene B4 (LTB4) were performed on synovial fluid from normal middle carpal joints of 10 horses, and from 30 middle carpal or antebrachiocarpal joints of horses affected by degenerative joint disease and chip fractures to compare the concentrations of inflammatory mediators. Significantly greater concentrations of PGE2 were detected in fluid from affected than from control joints, but there were no significant differences in the mean concentrations of PGF2 alpha, 6-keto-PGF1 alpha, and LTB4.

Animals↗
PubMed1996

Effect of polyaspartic acid on pharmacokinetics of gentamicin after single intravenous dose in the dog.

The effects of poly-L-aspartic acid on the pharmacokinetics of gentamicin were examined by using a randomized crossover trial design with the dog. When analyzed according to a three-compartment open model, poly-L-aspartic acid reduced some first-order rate equation constants (A3, lambda 1, and lambda 3), the deep peripheral compartment exit microconstant (k31), the elimination rate constant (k(el)), and the area under the concentration-time curve from 0 to 480 h (AUC0-480) (0.21-, 0.60-, 0.26-, 0.27-, 0.72-, and 0.76-fold, respectively; P < 0.05) but increased the volume of distribution at steady state (Vss), the volume of distribution calculated by the area method (V(area)), the apparent volume of the peripheral compartment (Vp), and all mean time parameters. These results suggested that poly-L-aspartic acid increased the distribution of gentamicin to or binding within the deep peripheral compartment and that poly-L-aspartic acid may have delayed gentamicin transit through the peripheral tissues. In contrast, poly-L-aspartic acid did not alter pharmacokinetic parameters relevant to the central or shallow peripheral compartments to a clinically significant extent. Although gentamicin's pharmacokinetic parameters of relevance to therapeutic drug monitoring were not directly altered, this study has provided pharmacokinetic evidence that poly-L-aspartic acid alters the peripheral distribution of gentamicin. This pharmacokinetic interaction occurred after a single intravenous dose of each drug. Therefore, this interaction should be investigated further, before polyaspartic acid can be considered for use as a clinical nephroprotectant.

Animals↗
PubMed1995

The effects on the pharmacokinetics of intravenous ceftiofur sodium in dairy cattle of simultaneous intravenous acetyl salicylate (aspirin) or probenecid.

Ceftiofur sodium is a third-generation cephalosporin antibiotic. It is possible that non-steroidal anti-inflammatory drugs such as acetyl salicylate (aspirin) may be used concomitantly with ceftiofur sodium in dairy cattle. Therefore this study evaluated potential pharmacokinetic interactions between ceftiofur sodium and aspirin. In addition, this study evaluated the potential for interaction between ceftiofur and its active metabolites and the organic anion transporter. The organic anion transporter substrate used in this evaluation was probenecid. Ten healthy, non-pregnant, non-lactating dairy cows were used in a randomized complete three-way crossover design. In repeated experiments all cows were administered: (1) 2 mg of ceftiofur sodium per kg body weight by intravenous bolus or (2) 10 mg of probenecid per kg body weight by intravenous bolus, followed immediately by 2 mg of ceftiofur sodium per kg body weight by intravenous bolus or (3) 26 mg of aspirin per kg body weight by intravenous bolus, followed immediately by 2 mg of ceftiofur sodium per kg body weight by intravenous bolus. For treatment with ceftiofur sodium alone, the mean volume of distribution at steady-state Vd(ss) was 0.2 +/- 0.06 L/kg, the mean volume of distribution by the area method Vd(area) was 0.38 +/- 0.22 L/kg, mean residence time (MRT) was 6.5 +/- 1.8 h, mean residence time in peripheral tissues (MRTp) was 2.6 +/- 1.0 h, total body clearance (Cl) was 0.032 +/- 0.013 L/kg/h and elimination rate constant (beta) was 0.097 +/- 0.044 h-1 (mean +/- standard deviation). No statistically significant changes were detected as a result of preceding treatment with aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

The disposition of gentamicin in equine plasma, synovial fluid and lymph.

Plasma (P), synovial fluid (SF) and lymph (L) concentrations of gentamicin were studied in two trials. A lymph vessel in the hindlimb was cannulated. The day after surgery (trial A), P and L samples were collected for 12 h after intravenous injection of gentamicin sulphate at 2.2 mg/kg dose rate. Approximately 48 h after surgery (trial B), the fetlock joint of the cannulated hindlimb was catheterized and P, SF and L samples collected for 12 h after a similar intravenous injection. The kinetic parameters were similar to those in other reports and did not differ between trials (P < 0.05). The P, L and SF disposition profiles were similar. The 95% confidence interval for P & L concentrations overlapped 2-3 h after injection. Thereafter, parallelism between L and P concentrations was observed, but L concentrations were on average 60% higher than P concentrations, and elimination from L was slower than from P. The mean L/SF and P/SF ratios were 1.54 +/- 0.2 and 1.25 +/- 0.2, 2-4 h after injection. Gentamicin elimination from SF appeared to be slower than from L and P. Lymph cannulation is a viable technique for antibiotic disposition studies. A sample of any of the fluids 3 h after injection was representative of the others. While SF concentrations were of limited value for predicting tissue fluid (L) concentrations 3-8 after injection, P concentrations were a useful index.

Animals↗