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  • Author or Editor: Jeff R. Wilcke x
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Summary

The disposition of clorazepate, a benzodiazepine anticonvulsant, was determined in dogs after administration of a single oral dose of clorazepate (2 mg/kg of body weight) and after oral administration of clorazepate (2 mg/kg, q 12 h) concurrently with phenobarbital (5 mg/kg, q 12 h) for 44 consecutive days. Serum concentrations of nordiazepam, the active metabolite of clorazepate, were measured. After a single oral dose of clorazepate, maximal nordiazepam concentrations ranged from 569.6 to 1,387.9 ng/ml (mean, 880.2 ± 248.9 ng/ml) and were detected 16.8 to 131.4 minutes (mean, 85.2 ± 36 minutes) after dosing. After administration of phenobarbital for 44 consecutive days, maximal nordiazepam concentrations were significantly (P < 0.01) lower, ranging from 209.6 to 698.5 ng/ml (mean, 399.3 ± 155.6 ng/ml) at 68.4 to 145.8 minutes (mean, 93 ± 25.8 minutes) after dosing. Mean area under the curve (AUC) on day 1 (mean, 3.37 ± 0.598 ng·min/ml) was significantly (P < 0.001) greater than AUC on day 44 (1.66 ± 0.308 ng·min/ml). Oral clearance was significantly (P < 0.01) greater on day 44 (12.44 ± 2.55 ml/min/kg), compared with that on day 1 (6.16 ± 1.35 ml/min/kg). Values for area under the first moment curve, oral volume of distribution, mean residence time, and elimination half-life were not significantly altered by concurrent administration of phenobarbital.

Administration of phenobarbital altered the disposition of clorazepate such that the amount of nordiazepam in circulation during each dose interval was significantly reduced. Adequate control of seizures in epileptic dogs, therefore, may require higher dosages of clorazepate when it is coadministered with phenobarbital.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine pharmacokinetic variables that describe disposition of ketoprofen after its IV administration to foals < 24 hours old.

Animals

6 healthy foals (1 male and 5 females); mean age, 12.5 (range, 8.5 to 17) hours at time of dose administration.

Procedure

Ketoprofen was administered IV to foals at a dosage of 2.2 mg/kg of body weight. Ketoprofen concentration in plasma samples was analyzed, using high-performance liquid chromatography. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined times during a 48-hour period. Samples were centrifuged, and plasma was frozen at −70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by use of Akaike's information criterion analysis.

Results

Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance (normalized for body weight) was significantly lower than that determined for adult horses. Volume of distribution (normalized for body weight) was larger than that determined for adult horses. Mean (harmonic) plasma half-life for healthy foals < 24 hours old was 4.3 hours.

Clinical Relevance

Although additional factors, such as dehydration or sepsis, must be considered on a case-by-case basis, the dose of ketoprofen administered to foals < 24 hours old should be different from the dose administered to adult horses. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to produce comparable therapeutic concentrations; longer dose intervals, based on clinical response, would be necessary to avoid drug toxicity. (Am J Vet Res 1998;59:290–292)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine pharmacokinetic variables that describe the disposition of flunixin after IV administration of flunixin meglumine to foals < 24 hours old.

Animals

6 healthy foals, 2 males and 4 females (mean age, 11.6 hours; range, 6 to 22.5 hours).

Procedure

Flunixin (as flunixin meglumine) was administered to foals at a dosage of 1.1 mg/kg of body weight. Flunixin concentration in plasma samples was analyzed, using gas chromatography/mass spectroscopy. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined intervals over a 48-hour period. Samples were centrifuged, and plasma was frozen at −70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by Akaike's information criterion analysis.

Results

Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance was significantly lower than that determined for older foals and adult horses. Volume of distribution was larger than that determined for adults. Mean plasma halflife for healthy foals < 24 hours old was 8.5 hours.

Conclusions and Clinical Relevance

Although additional factors (eg, dehydration or sepsis) must be considered on a case-by-case basis, flunixin meglumine should be administered differently to foals < 24 hours old, compared with adults. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to induce comparable therapeutic concentrations; longer dose intervals, on the basis of clinical response, would be necessary to avoid drug toxicity. (Am J Vet Res 1996;57:1759–1761)

Free access
in American Journal of Veterinary Research

Summary

Single doses (2.2 mg/kg of body weight) of phenylbutazone (pbz) were administered iv to 6 neonatal horses (5 to 17 hours old at time of dosing). Plasma concentrations of pbz and its metabolite oxyphenbutazone were monitored serially for 120 hours after drug administration. Pharmacokinetic variables were calculated, using 1- and 2-compartment open models. Descriptive equations from the best model for each foal were then used to derive model-independent variables describing pbz disposition. Median volume of distribution at steady-state was 0.274 L/ kg (range, 0.190 to 0.401 L/kg). Median terminal half-life was 7.4 (6.4 to 22.1) hours, and median total plasma clearance of pbz for foals in this study was 0.018 L/kg/h (range, 0.013 to 0.038 L/kg/h). Volume of distribution was larger, half-life was longer, and total clearance was lower, compared with similar values reported for administration of pbz to adult horses.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether a limited sampling time method based on serum iohexol clearance (Cliohexol) would yield estimates of glomerular filtration rate (GFR) in clinically normal horses similar to those for plasma creatinine clearance (Clcreatinine).

Animals—10 clinically normal adult horses.

Procedures—A bolus of iohexol (150 mg/kg) was administered IV, and serum samples were obtained 5, 20, 40, 60, 120, 240, and 360 minutes after injection. Urinary clearance of exogenous creatinine was measured during three 20-minute periods. The GFR determined by use of serum Cliohexol and plasma Clcreatinine was compared with limits of agreement plots.

Results—Values obtained for plasma Clcreatinine ranged from 1.68 to 2.69 mL/min/kg (mean, 2.11 mL/min/kg). Mean serum Cliohexol was 2.38 mL/min/kg (range, 1.95 to 3.33 mL/min/kg). Limits of agreement plots indicated good agreement between the methods.

Conclusions and Clinical Relevance—Use of serum Cliohexol yielded estimates of GFR in clinically normal adult horses similar to those for plasma Clcreatinine. This study was the first step in the evaluation of the use of serum Cliohexol for estimating GFR in adult horses.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether pharmacokinetic analysis of data derived from a single IV dose of iohexol could be used to predict creatinine clearance and evaluate simplified methods for predicting serum clearance of iohexol with data derived from 2 or 3 blood samples in clinically normal foals.

Animals—10 healthy foals.

Procedure—Serum disposition of iohexol and exogenous creatinine clearance was determined simultaneously in each foal (5 males and 5 females). A 3-compartment model of iohexol serum disposition was selected via standard methods. Iohexol clearance calculated from the model was compared with creatinine clearance. Separate limited-sample models were created with various combinations of sample times from the terminal slope of the plasma versus time profile for iohexol. Correction factors were determined for the limited-sample models, and iohexol clearance calculated via each method was compared with exogenous creatinine clearance by use of method comparison techniques.

Results—Mean exogenous creatinine clearance was 2.17 mL/min/kg. The disposition of iohexol was best described by a 3-compartment open model. Mean clearance value for iohexol was 2.15 mL/min/kg and was not significantly different from mean creatinine clearance. A method for predicting serum iohexol clearance based on a 2-sample protocol (3- and 4-hour samples) was developed.

Conclusions and Clinical Relevance—Iohexol clearance can be used to predict exogenous creatinine clearance and can be determined from 2 blood samples taken after IV injection of iohexol. Appropriate correction factors for adult horses and horses with abnormal glomerular filtration rate need to be determined. (Am J Vet Res 2003;64:1486–1490)

Full access
in American Journal of Veterinary Research