Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose

Pinto, Nelson; Schumacher, Jim; Taintor, Jennifer; DeGraves, Fred J.; Duran, Sue H.; Boothe, Dawn M.

doi:10.1111/j.2042-3306.2010.00144.x

Cited by 17 publications

(20 citation statements)

References 21 publications

(74 reference statements)

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“…All three input curves differ only in the first 7 min period while following identical decay variation in the subsequent 7-150 min interval. The foregoing peak concentrations in serum are in general agreement with other works reporting temporal variation of antibiotic concentrations in blood (Pinto et al, 2011;Shi et al, 2010;Yates et al, 1983). These latter studies are subsequently used to extrapolate the input source curve from 150 min (38.7 mg/L) to 10 h (1.35 mg/L) ( The blood-disc partition coefficient is 0.37 at the CEP boundary and 0.41 at the OA periphery (Maroudas, 1970(Maroudas, , 1976Urban et al, 1982), reducing thus the prescribed sources (Fig.…”

Section: Finite Element Modelsupporting

confidence: 92%

“…We take account of the transient supply source since solute concentration in the circulation falls exponentially after intravenous injection. The transient supply source via blood vessels is set according to earlier in vivo measurements of cephazolin in human patients (Walters et al, 2006c), of cefotetan antibiotic in human volunteers (Shi et al, 2010;Yates et al, 1983), and of amikacin antibiotic in horses (Pinto et al, 2011). Results for 10 h post-intravenous injection are compared with in vivo measurements (Walters et al, 2006c).…”

Section: Introductionmentioning

confidence: 99%

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Computational pharmacokinetics of solute penetration into human intervertebral discs—Effects of endplate permeability, solute molecular weight and disc size

Motaghinasab

Shirazi-Adl

Urban

et al. 2012

Journal of Biomechanics

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Section: Finite Element Modelsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Computational pharmacokinetics of solute penetration into human intervertebral discs—Effects of endplate permeability, solute molecular weight and disc size

Motaghinasab

Shirazi-Adl

Urban

et al. 2012

Journal of Biomechanics

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“…1C-I) (Currier et al, 1994; Pinto et al, 2011; Shi et al, 2010; Walters et al, 2006a). The blood-disc partition coefficient was assumed to be unity for each antibiotic studied, and the antibiotic concentration was neglected in Eq (5) due to its low concentration.…”

Section: Methodsmentioning

confidence: 99%

Kinetics of charged antibiotic penetration into human intervertebral discs: A numerical study

Zhu

Gao

et al. 2016

Journal of Biomechanics

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Little quantitative information exists on the kinetics of charged antibiotic penetration into human intervertebral discs (IVD). This information is crucial for determining the dosage to use, timing of administration, and duration of treatment for infected IVDs. The objective of this study was to quantitatively analyze the transport of various charged antibiotics into human lumbar IVDs. Penetration of charged and uncharged antibiotics into a human lumbar disc was analyzed using a 3D finite element model. The valence (z) of the electrical charge of antibiotics varied from z=+2 (positively charged) to z=−2 (negatively charged). An uncharged antibiotic (z=0) was used as a control. Cases with intravenous (IV) administrations of different charged antibiotics were simulated. Our results showed that the electrical charge had great effects on kinetics of an antibiotic penetration into the IVD; with higher concentrations and uptakes for positively charged antibiotics than those for negatively charged ones. This study provides quantitative information on selecting antibiotics for treating intervertebral disc infections.

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“…Pharmacokinetics of various solutes have been examined in a wide range of species from animals as large as horses [1,2] to sheep [3,4], dogs [5,6], rabbits [7][8][9] and finally to animals as small as rats and mice [10,11]. Apart from inherent inter-and intra-species differences in cell type, tissue composition and mechanical properties, there is a huge difference between the disc sizes among these species.…”

Section: Introductionmentioning

confidence: 99%

Disc size markedly influences concentration profiles of intravenously administered solutes in the intervertebral disc: a computational study on glucosamine as a model solute

et al. 2013

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Purpose Tests on animals of different species with large differences in intervertebral disc size are commonly used to investigate the therapeutic efficacy of intravenously injected solutes in the disc. We hypothesize that disc size markedly affects outcome. Methods Here, using a small non-metabolized molecule, glucosamine (GL) as a model solute, we calculate the influence of disc size on transport of GL into rat, rabbit, dog and human discs for 10 h post intravenous-injection. We used transient finite element models and considered an identical GL supply for all animals. Results Huge effects of disc size on GL concentration profiles were found. Post-injection GL concentration in the rat disc reached 70 % blood concentration within 15 min but remained below 10 % in the human disc nucleus throughout. The GL rapidly penetrated post-injection into smaller discs resulting in homogeneous concentrations. In contrast, GL concentration, albeit at much lower levels, increased with time in the human disc with a small outward flux at the annulus periphery at longer periods. Conclusions Changes in the disc size hugely influenced GL concentrations throughout the disc at all regions and times. Increases in administered dose can neither remedy the very low concentration levels in the disc center in larger human disc at early post-injection hours nor alter the substantial differences in concentration profiles estimated among various species. The size effect will only be exacerbated as molecular weight of the solute increases and as the endplate calcifies. Extrapolation of findings from animal to human discs on the efficacy of intravenously administered solutes must proceed with great caution.

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Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose

Abstract: Low dose amikacin (10 mg/kg bwt) administered once a day in mature horses may be efficacious against susceptible microorganisms.

Cited by 17 publications

References 21 publications

Computational pharmacokinetics of solute penetration into human intervertebral discs—Effects of endplate permeability, solute molecular weight and disc size

Computational pharmacokinetics of solute penetration into human intervertebral discs—Effects of endplate permeability, solute molecular weight and disc size

Kinetics of charged antibiotic penetration into human intervertebral discs: A numerical study

Disc size markedly influences concentration profiles of intravenously administered solutes in the intervertebral disc: a computational study on glucosamine as a model solute

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