Biomedical subjects

Y Salmon

Publications and source records attributed to Y Salmon.

17 recordsLinked to original sources

PubMed2001

[Chronic experimental bacteremia in Yucatan micropigs].

The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.

Acute Kidney Injury↗

PubMed1997

Pharmacokinetic interaction between itraconazole and ceftriaxone in Yucatan miniature pigs.

Since ceftriaxone and itraconazole are highly protein bound, are excreted via a biliary pathway, and are in vitro modulators of the efflux pump P glycoprotein, a pharmacokinetic interaction between these antimicrobial agents can be hypothesized. Therefore, we evaluated the pharmacokinetics of itraconazole and ceftriaxone alone and in combination in a chronic model of catheterized miniature pigs. Itraconazole does not influence ceftriaxone kinetic behavior. The mean areas under the concentration-time curve (AUC) were 152.2 microg x h/ml (standard deviation [SD], 22.5) and 129.2 microg x h/ml (SD, 41.2) and the terminal half-lives were 1.1 h (SD, 0.3) and 0.9 h (SD, 0.2) when ceftriaxone was given alone and combined with itraconazole, respectively. Regarding itraconazole kinetics, ceftriaxone was shown to alter the disposition of the triazole. Contrary to what was expected, the AUC (from 0 to 8 h) decreased from 139.3 ng h/ml with itraconazole alone to 122.7 ng h/ml with itraconazole and ceftriaxone combined in pig 1, from 398.5 to 315.7 ng x h/ml in pig 2, and from 979.6 to 716.6 ng x h/ml in pig 3 (P of <0.01 by analysis of variance).

Administration, Oral↗

PubMed1997

[In vivo pharmacokinetic of amikacin and its pharmacodynamic in combination with cefepime, cefpirome and meropenem in an in vitro/ex vivo micropig model].

Three female Yucatan micropigs were included and received a single dose of amikacin (15 mg/kg) by short infusion (30 min) combined either with a single dose of cefepime or cefpirome (30 mg/kg/12 h) or meropenem (7 mg/kg/8 h). The beta-lactams were administered either by intravenous intermittent injection or by continuous infusion. The mean elimination half-life and clearance value of amikacin were 1.88 h and 2.15 ml/min.kg-1 respectively. These pharmacokinetic parameters were similar to those obtained in man (t1/2 = 2,42 h et Cl = 1,61 ml/min kg-1). Furthermore, they were not affected by coadministration of cefepime, cefpirome and to meropenem. While resistant to cefepime, cefpirome and amikacin, Klebsiella pneumoniae producing ESBL was susceptible to combination of these cephalosporins with amikacin in an in vitro/ex vivo micropig model. For the six dosage regimens used in this study, the killing activities were similar and resulted in at least 4 log decrease at 6 h after drug exposure. For antimicrobial combination consisting of bolus dosing of amikacin plus continuous infusion of cefepime or cefpirome, the 12 h serum bactericidal titers (SBTs) were 1:8 for cefepime and 1:2 for cefpirome dosage regimen. When each drug administered intermittently, the 12 h SBTs were 1:4 for cefepime and 1:2 for cefpirome. The 8 h SBTs for dosing schedule containing meropenem combined with amikacin were 1:4 and 1:16 after 30 min short infusion and continuous infusion respectively. In conclusion, our study showed that the micropig model is a reliable model for pharmacokinetic investigation of amikacin. It was concluded that beta-lactam antibiotics tested with amikacin may be coadministered by using the standard recommended dosing regimen of amikacin. Continuous infusion of beta-lactams combined with once dosing of amikacin seems to be as or more effective than intermittent injection of each drug.

Amikacin↗

PubMed1996

Pharmacokinetic interaction between itraconazole and rifampin in Yucatan miniature pigs.

The objective of this study was to examine the effects of rifampin on itraconazole pharmacokinetics, at steady state, in three Yucatan miniature pigs. Daily for 3 weeks, the pigs received 200 mg of itraconazole orally at the beginning of each meal, and for the following 2 weeks they received itraconazole orally combined with intravenous administration of rifampin at 10 mg/kg/day. Coadministration of rifampin resulted in an 18-fold decrease in the maximum concentration of itraconazole in serum, from 113.0 (standard deviation [SD] 17.2) to 6.2 (SD, 3.9) ng/ml and a 22-fold decrease in the area under the concentration-time curve, from 1,652.7 (SD, 297.7) to 75.6 (SD, 30.0) ng.h/ml. The active metabolite of itraconazole, hydroxyitraconazole, was undetectable. This study demonstrates that rifampin affects itraconazole kinetics considerably at steady state in this miniature-pig model, probably by inducing hepatic metabolism of itraconazole.

Animals↗

PubMed1996

[Model of a miniature pig catheterized for pharmacokinetic and pharmacodynamic studies of anti-infective agents].

The miniature pig exhibits physiological and anatomical similarities to man. In addition, its reduced size and its docility make it appropriate for laboratory use. Curiously, this model remains seldom used in experimental pharmacokinetics. We present here in a chronic model of catheterized micropig allowing long term investigations of antiinfective agents. We work with Yucatan adult female micropigs weighing between 20 and 40kg. A catheter (60 cm x 2 mm) is placed in the external jugular vein under general anaesthesia and exits in the midline dorsal neck. The catheter is flushed every two days with heparinized saline to retain its potency. At the time of kinetic studies, the antiinfective agent is injected in an ear vein. Blood samples are obtained using the jugular catheter. The mean time of viability of the device is 13 weeks (SD: 10 weeks). Thrombosis was the main cause of arrest of the model. In conclusion, this chronic model of catheterized micropig is suitable for long term pharmacokinetic and pharmacodynamic investigations of antiinfective agents.

Adult↗

PubMed1996

[Pharmacokinetic interaction between itraconazole and rifampin in Yucatan miniature pigs].

The objective of this study was to examine the effects of rifampin on itraconazole pharmacokinetics, at steady state, in three Yucatan miniature pigs. The pits received daily during three weeks oral itraconazole at a dosage of 200 mg at the beginning of the meal, then during the next two weeks oral itraconazole combined with an intravenous administration of rifampin at a dosage of 10 mg/kg/day. The coadministration of rifampin resulted in a 18 fold decrease of the Cmax of itraconazole [from 113.0 (SD: 17.2) to 6.2 ng/ml (SD: 3.9)], and in a 22 fold decrease of the AUC [from 1652.7 (SD: 297.7) to 75.6 ng.h/ml (SD: 30.01)]. The active metabolite of itraconazole, hydroxyitraconazole, was undetectable. This study demonstrates that rifampin considerably affects itraconazole kinetics at steady-state in this model of micropig, probably by inducing the hepatic metabolism of itraconazole.

Administration, Oral↗

PubMed1995

[Intravenous anesthesia in the horse: comparison of xylazine-ketamine and xylazine-tiletamine-zolazepam combinations].

Intravenous anesthesia in the horse: Comparison of xylazine-ketamine and xylaxine-tiletamine-zolazepam combinations. Six healthy adult horses were anesthetized twice at random with following intravenous combinations: 1.1 mg/kg of body weight (BW) of xylazine followed by 2.2 mg/kg BW of ketamine (X-K) and 1.1 mg/kg BW of xylazine followed by 1.65 mg/kg BW of tiletamine-zolazepam (X-TZ). The modifications of some cardiorespiratory parameters and the duration of anesthesia were evaluated and compared for the 2 protocols used. Few significant differences were observed between the 2 protocols in regard to the cardiorespiratory parameters measured. The respiratory rate was lower (7 breaths per minute) and the heart rate was higher (34 beats per minute) with the X-TZ combination. The duration of anesthesia with this technique was 33 +/- 3 minutes (X +/- Sx) and longer than with X-K (18 +/- minutes (X +/- Sx)). Superficial analgesia lasted 14,5 +/- 3 minutes with the X-K combination and 31,7 +/- 3,2 minutes for the X-TZ combination. The 2 protocols are associated with a reduction of PaO2.

Anesthesia, Intravenous↗

PubMed1994

Head and neck tumors after energetic proton irradiation in rats.

This is a two-year progress report on a life span dose-response study of brain tumor risk at moderate to high doses of energetic protons. It was initiated because a joint NASA/USAF life span study of rhesus monkeys that were irradiated with 55-MeV protons (average surface dose, 3.5 Gy) indicated that the incidence of brain tumors per unit surface absorbed dose was over 19 times that of the human tinea capitis patients whose heads were exposed to 100 kv x-rays. Examination of those rats that died in the two-year interval after irradiation of the head revealed a linear dose-response for total head and neck tumor incidence in the dose range of 0-8.5 Gy. The exposed rats had a greater incidence of pituitary chromophobe adenomas, epithelial and mesothelial cell tumors than the unexposed controls but the excessive occurrence of malignant gliomas that was observed in the monkeys was absent in the rats. The estimated dose required to double the number of all types of head and neck tumors was 5.2 Gy. The highest dose, 18 Gy, resulted in high mortality due to obstructive squamous metaplasia at less than 50 weeks, prompting a new study of the relative biological effectiveness of high energy protons in producing this lesion.

Adenoma↗

PubMed1993

Implantation of a programmable atrioventricular pacemaker in a donkey with complete atrioventricular block and syncope.

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Adams-Stokes Syndrome↗

PubMed1992

Procedures of choice in renal nuclear medicine.

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Radioisotope Renography↗

PubMed1990

Temporal behavior of peripheral organ distribution volume in mammillary systems. I. A new tool for in vivo tracer kinetic analysis.

In complex mammillary compartmental systems, the kinetic solutions for central and peripheral compartments are sums of too many exponentials to be accurately analyzed without very sophisticated mathematical tools. Our data show the peripheral organ distribution volume (PODV) kinetics to exhibit systematic time behavior depending on its mode of relation with plasma: linear increase for irreversible transfer, uniexponential function growing toward as asymptotic value for reversible transfer. Statistical analysis of our kinetic data shows that no other significant information can be extracted at least inside the time and statistical noise limits of our investigation. After intravenous injection of a diffusible tracer, the total activity in any region of interest (ROI) in the body is the sum of various components and, under certain conditions, PODV transformation easily allows their separation. Our simple non-compartmental model provides a useful tool for quantitative tracer analysis in nuclear medicine.

Extracellular Space↗

PubMed1990

Temporal behavior of peripheral organ distribution volume in mammillary systems. II. Application to background correction in separate glomerular filtration rate estimation in man.

An original approach to background subtraction is presented for 99mTc-DTPA separate glomerular filtration rate (SGFR) estimation in man. The method is based on the properties of the peripheral organ distribution volume (PODV) in mammillary systems. These PODV properties allow easy separation of the components of the renogram, i.e., interstitial fluid, plasma and renal activities. The proposed algorithm takes advantage of the linear time dependence of the kidney distribution volume, during the renal uptake phase, to correct for the plasma residual activity, which always remains after classical background correction. Theoretically, the ratio between kidney uptake and SGFR should be identical for both left and right kidneys, even for very asymmetrical kidney functions. This is best verified when the proposed plasma residual activity correction is applied.

Algorithms↗

PubMed1983