Biomedical subjects

Hervé P Lefebvre

Publications and source records attributed to Hervé P Lefebvre.

9 recordsLinked to original sources

PubMed2006

Disposition of plasma creatinine in non-azotaemic and moderately azotaemic cats.

The objectives of this study were to compare assay methods for plasma creatinine (Pl-creat) in cats and to describe the disposition of creatinine and iohexol in 12 healthy and moderately azotaemic cats. Exogenous creatinine and iohexol were injected simultaneously by intravenous bolus, and repeated blood samples were taken to determine the pharmacokinetic parameters of each marker. Pl-creat was assayed by high-performance liquid chromatography (HPLC), Jaffé and enzymatic methods. The enzymatic method was shown to be more reliable than the Jaffé method. Two stereoisomers, exo- and endo-iohexol were identified. The plasma clearance of creatinine (2.3+/-0.66 ml/min/kg) was significantly higher (P<0.001) than that of exo-iohexol (1.7+/-0.40 ml/min/kg). The volume of distribution (447+/-97 ml/kg) and elimination half-life (181+/-77 min) of creatinine were also higher (P<0.001) than those of exo- and endo-iohexol. The estimated daily endogenous production of creatinine was 65+/-23 mg/kg. None of the pharmacokinetic parameters was changed by the azotaemic status of the animals.

Animals↗

PubMed2006

Plasma pharmacokinetics of alfaxalone in dogs after an intravenous bolus of Alfaxan-CD RTU.

OBJECTIVE: To determine the pharmacokinetic parameters of alfaxalone in dogs after the intravenous (IV) administration of clinical and supra-clinical doses of a 2-hydroxypropyl-beta-cyclodextrin (HPCD) alfaxalone formulation (Alfaxan-CD RTU). EXPERIMENTAL DESIGN: Prospective two-period crossover design. Animals Eight (four male and four female) young adult healthy Beagle dogs. Methods The steroid anaesthetic alfaxalone was administered IV at two doses in a crossover design (2 and 10 mg kg(-1)) with a washout period of 21 days. Blood samples were collected before and up to 8 hours after dosing. Plasma concentrations of alfaxalone were assayed using a liquid chromatograph/mass selective detector technique and analyzed to estimate the main pharmacokinetic parameters by noncompartmental analysis. Results were expressed as mean +/- SD. RESULTS: The mean duration of anaesthesia from endotracheal intubation to extubation was 6.4 +/- 2.9 and 26.2 +/- 7.5 minutes, for the 2 and 10 mg kg(-1) doses, respectively. The plasma clearance of alfaxalone for the 2 and 10 mg kg(-1) doses differed statistically at 59.4 +/- 12.9 and 52.9 +/- 12.8 mL kg(-1) minute(-1), respectively (p = 0.008) but this difference was deemed clinically unimportant; the harmonic mean plasma terminal half-lives (t(1/2)) were 24.0 +/- 1.9 and 37.4 +/- 1.6 minutes respectively. The volume of distribution was between 2 and 3 L kg(-1) and did not differ between the two doses. No sex effect was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone, as an HPCD formulation (Alfaxan-CD RTU) administered in the dog provides rapid and smooth induction of anaesthesia, satisfactory conditions for endotracheal intubation and a short duration of anaesthesia. There was no clinically significant modification of the pharmacokinetic parameters between sexes and between the clinical (2 mg kg(-1)) and supra-clinical (10 mg kg(-1)) doses.

Anesthesia, General↗

PubMed2005

Effect of marbofloxacin on cardiovascular variables in healthy isoflurane-anesthetized dogs.

OBJECTIVE: To study the hemodynamic effects of marbofloxacin (MBF) in isoflurane-anesthetized dogs. ANIMALS: 6 healthy 8-month-old Beagles. PROCEDURE: Anesthesia was induced with sodium thiopental and maintained with isoflurane. Cardiovascular variables were monitored throughout anesthesia. Marbofloxacin was administered by an IV bolus at 2 mg/kg, followed 10 minutes later by an infusion at a rate of 40 mg/kg/h for 30 minutes (total dose, 20 mg/kg). Plasma MBF concentrations were measured by high-performance liquid chromatography. RESULTS: The mean peak concentration during MBF infusion was 34.2 +/- 6.4 microg/mL. The IV administration of the MBF bolus did not alter any cardiovascular variable in isoflurane-anesthetized dogs. Significant changes were found during infusion when a cumulative dose of 12 mg/kg had been given. The maximal decreases observed at the end of the infusion were 16% in heart rate, 26% in systolic left ventricular pressure, 33% in systolic aortic pressure, 38% in diastolic aortic pressure, 29% in cardiac output, and 12% in QT interval. All dogs recovered rapidly from anesthesia at the end of the experiment. CONCLUSIONS AND CLINICAL RELEVANCE: MBF may safely be used at 2 mg/kg IV in isoflurane-anesthetized dogs, and significant adverse cardiovascular effects are found only when 6 to 8 times the recommended dose is given.

Analysis of Variance↗

PubMed2005

Use of quantitative two-dimensional color tissue Doppler imaging for assessment of left ventricular radial and longitudinal myocardial velocities in dogs.

OBJECTIVE: To determine left ventricular free wall (LVFW) radial and longitudinal myocardial contraction velocities in healthy dogs via quantitative 2-dimensional color tissue Doppler imaging (TDI). ANIMALS: 100 dogs. PROCEDURE: TDI was used by a single trained observer to measure radial and longitudinal myocardial movement in the LVFW. Radial myocardial velocities were recorded in segments in the endocardial and epicardial layers of the LVFW, and longitudinal velocities were recorded in segments at 3 levels (basal, middle, apical) of the LVFW. RESULTS: LVFW velocities were higher in the endocardial layers than in the epicardial layers. Left ventricular free wall velocities were higher in the basal segments than in the middle and apical segments. Radial myocardial velocity gradients, defined as the difference between endocardial and epicardial velocities, were (mean +/- SD) 2.5 +/- 0.8 cm/s, 3.8 +/- 1.5 cm/s, and 2.3 +/- 0.9 cm/s in systole, early diastole, and late diastole, respectively. Longitudinal myocardial velocity gradients, defined as the difference between basal and apical velocities, were 5.9 +/- 2.2 cm/s, 6.9 +/- 2.5 cm/s, and 4.9 +/- 1.7 cm/s in systole, early diastole, and late diastole, respectively. A breed effect was detected for several systolic and diastolic TDI variables. In all segments, systolic velocities were independent of fractional shortening. CONCLUSIONS AND CLINICAL RELEVANCE: LVFW myocardial velocities decreased from the endocardium to the epicardium and from base to apex, thus revealing intramyocardial radial and longitudinal velocity gradients. These indices could enhance conventional echocardiographic analysis of left ventricular function in dogs. Breed-specific reference intervals should be defined.

Age Factors↗

PubMed2004

Quantification, repeatability, and reproducibility of feline radial and longitudinal left ventricular velocities by tissue Doppler imaging.

OBJECTIVE: To measure the radial and longitudinal velocities of several myocardial segments of the left ventricular wall by use of tissue Doppler imaging (TDI) in healthy cats and determine the repeatability and reproducibility of the technique. ANIMALS: 6 healthy cats. PROCEDURE: 72 TDI examinations were performed on 4 days by the same trained observer. Radial parameters included left endocardial and epicardial myocardial velocities. Longitudinal parameters included left basal, middle, and apical myocardial velocities. RESULTS: All velocity profiles had 1 positive systolic wave (S) and 2 negative diastolic waves (E and A). Myocardial velocities were higher in the endocardial than epicardial segments during the entire cardiac cycle (systolic wave S, 4.4 +/- 0.82 and 1.9 +/- 0.55; diastolic wave E, 9.7 +/- 1.70 and 2.2 +/- 0.74; and diastolic wave A, 5.1 +/- 1.56 and 1.4 +/- 0.76, respectively). Velocities were also higher in the basal than in the apical segments (systolic wave S, 4.7 +/- 0.76 and 0.2 +/- 0.11; diastolic wave E, 9.7 +/- 1.36 and 0.5 +/- 0.17; and diastolic wave A, 3.7 +/- 1.51 and 0.2 +/- 0.13, respectively). The lowest within-day and between-day coefficients of variation were observed in endocardial segments (8.2% and 6.5% for systolic wave S and diastolic wave E, respectively) and in the basal segment in protodiastole (5.5%). CONCLUSIONS AND CLINICAL RELEVANCE: Repeatability and reproducibility of TDI were adequate for measurement of longitudinal and radial left ventricular motion in healthy awake cats. Validation of TDI is a prerequisite before this new technique can be recommended for clinical use.

Analysis of Variance↗

PubMedDate not supplied

Plasma exogenous creatinine clearance test in dogs: comparison with other methods and proposed limited sampling strategy.

Plasma clearance of creatinine was evaluated for assessment of glomerular filtration rate (GFR) in dogs. In 6 healthy dogs (Experiment 1), we determined 24-hour urine clearance of endogenous creatinine, plasma, and urine clearances of exogenous creatinine administered at 40, 80, and 160 mg/kg in a crossover design (linearity study), plasma iothalamate clearance, and plasma and urine clearances of 14C-inulin. In Experiment 2, plasma creatinine and iothalamate clearances were compared, and a linearity study was performed as for Experiment 1 in 6 dogs with surgically induced renal impairment. Experiment 3 compared plasma creatinine clearance with plasma iothalamate clearance before and 3 weeks after induction of moderate renal impairment in 6 dogs. Plasma creatinine clearances were calculated by both noncompartmental and compartmental analyses. In Experiment 1, plasma inulin clearance was higher (P < .001) than other clearance values. Plasma creatinine clearances at the 3 dose rates did not differ from urine inulin clearance and each other. In Experiment 2, plasma creatinine clearances were about 14% lower than plasma iothalamate clearance (P < .05). In Experiment 3, decreases in GFR assessed by plasma clearances of iothalamate and creatinine were similar. Renal failure decreased the daily endogenous input rate of creatinine by 25%. Limiting sampling strategies for optimizing GFR calculation were proposed, allowing an error lower than 6.5% with 4 blood samples. These results suggest that determination of plasma creatinine clearance by a noncompartmental approach offers a reliable, inexpensive, rapid, and convenient means of estimating GFR in routine practice.

Animals↗

PubMedDate not supplied

Spontaneous feline hypertension: clinical and echocardiographic abnormalities, and survival rate.

Systemic hypertension was diagnosed in 58 of 188 untreated cats referred for evaluation of suspected hypertension-associated ocular, neurologic. cardiorespiratory, and urinary disease, or diseases frequently associated with hypertension (hyperthyroidism and chronic renal failure). Hypertensive cats were significantly older than normotensive subjects (13.0 +/- 3.5 years versus 9.6 +/- 5.0 years; P < .01), and had a greater prevalence of retinal lesions (48 versus 3%; P < .001), gallop rhythm (16 versus 0%; P < .001), and polyuria-polydipsia (53 versus 29%: P < .01). Blood pressure was significantly higher (P < .001) in cats with retinopathies (262 +/- 34 mm Hg) than in other hypertensive animals (221 +/- 34 mm Hg). Hypertensive cats had a thicker interventricular septum (5.8 +/- 1.7 versus 3.7 +/- 0.64 mm; P < .001) and left ventricular free wall (6.2 +/- 1.6 versus 4.1 +/- 0.51 mm; P < .001) and a reduced diastolic left ventricular internal diameter (13.5 +/- 3.2 versus 15.8 +/- 0.72 mm; P < .001) than control cats. Left ventricular geometry was abnormal in 33 of 39 hypertensive subjects. No significant difference was found in age or blood pressure at the initial visit between cats that died or survived over a 9-month period after initial diagnosis of hypertension. Mean survival times were not significantly different between hypertensive cats with normal and abnormal left ventricular patterns. Further prospective studies are needed to clearly identify the factors involved in survival time in hypertensive cats.

Aging↗

PubMedDate not supplied

Pharmacokinetic and pharmacodynamic parameters of ramipril and ramiprilat in healthy dogs and dogs with reduced glomerular filtration rate.

Ramipril, an angiotensin-converting enzyme (ACE) inhibitor for use in dogs, is converted in vivo to its active form, ramiprilat, which is eliminated in the bile and urine in the dog. The objective of this study was to assess the effect of renal impairment on the pharmacokinetics (PKs) and pharmacodynamics (PDs) of ramipril and ramiprilat. Ten adult Beagle dogs were used. PK/PD studies were performed before and after the induction of subclinical renal impairment. Ramiprilat was given at 0.25 mg/kg by a single IV bolus. After a 2-week washout period, ramipril was administered PO at 0.25 mg/kg once daily for 8 days. Ramipril and ramiprilat PKs were studied by using a physiologically based model. The relationship between free plasma ramiprilat concentration and ACE activity was described by using the fractional Hill model. Glomerular filtration rate was decreased by 58%. No biologically relevant changes in usual plasma variables were observed between the 1st and the 8th day of oral treatment with ramipril under either condition. After an IV bolus of ramiprilat, the only changes in renal-impaired dogs were a 14 and 49% decrease in clearance of the free fraction of ramiprilat (P < .01) and free plasma concentration required to produce 50% of the maximal effect (P < .05), respectively. After repeated PO administration of ramipril, there were no alterations in any of the PK and PD parameters in healthy or renal-impaired dogs. No adjustment of the recommended PO dosage of ramipril is needed in dogs with moderate renal impairment.

Administration, Oral↗

PubMedDate not supplied

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Animals↗