Absorption and Bioavailability of Glucosamine in the Rat

Ibrahim, Alyaa; Kohan, Hamed Gilzad; Aghazadeh‐Habashi, Ali; Jamali, Fakhreddin

doi:10.1002/jps.23145

Cited by 35 publications

(30 citation statements)

References 34 publications

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“…2) in accordance with post-intravenous injection measurement of GL concentration in plasma in studies using doses proportional to body weight [1,5,11]. Due to the linear relationship between the source input and concentration values, any changes in administered dose are expected to proportionally shift up or down the computed concentrations at all times.…”

Section: Discussionmentioning

confidence: 61%

“…1) is taken based on measurements as identical for all discs [1,5,11]. The intravenous administration of GL in rats and horses at 10-20 mg/Kg dose [1,11] and at 500 mg single dose in beagle dogs [5] resulted in nearly similar plasma GL concentration profiles assumed here. The simulated concentration profile in the current work reaches its peak of 100 mg/L at 30 s post injection and drops thereafter to 4 mg/L at 10 h (Fig.…”

Section: Finite Element Modelmentioning

confidence: 84%

“…Here we examined the effect of disc size on transport of GL into the disc following an intravenous injection calculated to provide an identical GL supply for the human, dog, rabbit and rat discs, as achieved in vivo by dosing animals according to body weight [1,5,11]. Results demonstrate the huge effect of inter-species changes in the disc size on GL concentration profiles.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…We calculated and compared GL penetration time-histories into the rat, rabbit, dog and human lumbar discs. The time-dependent concentration profiles at the surface of the disc, arising from the decay of GL concentration in the serum post-injection, were taken as identical for all species based on values reported in the literature [1,5,11,25]. We hypothesized that substantial differences in concentration profiles would arise due to inter-species differences in disc size and that these differences would persist despite alterations in administered doses.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 61%

Section: Finite Element Modelmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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Pharmacokinetics of nebivolol in the rat: low oral absorption, loss in the gut and systemic stereoselectivity

Sanaee

Neves

Lanchote

et al. 2013

Biopharm & Drug Disp

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Nebivolol is a third-generation β1-adrenoceptor blocker with β3 agonistic properties (AR). It has a low oral bioavailability that is speculated to be due to its hepatic first-pass metabolism. Inflammation is known to suppress the clearance of drugs with efficient hepatic metabolism. However, inflammation does not influence nebivolol clearance. Therefore, we looked into the mechanism involved in the drug's low bioavailability and stereoselectivity. Single 1 mg/kg i.v. or intraperitoneal (i.p.) or 2 mg/kg oral doses were administered to male Sprague-Dawley rats and the plasma nebivolol concentration was measured using chiral and achiral assays. The passage of nebivolol enantiomers through the gut was also measured using everted rat sacs. The serum protein binding of the enantiomers was studied in vitro using the ultrafiltration method. Plasma nebivolol concentrations were significantly lower after p.o., but not after i.p., compared with i.v. doses suggesting the gut as the site of pre-systemic loss. Approximately 50% of the enantiomers were lost during 90 min incubation in the presence of gut. Only 0.1% of the added drug crossed the gut wall with no evidence of stereoselectivity. Thus stereoselectivity in the pharmacokinetics of nebivolol (+ > -) is likely at the level of plasma protein binding. The low nebivolol bioavailability is due to its loss in the gut as well as its limited permeability through the intestinal wall.

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Glucosamine Dose/Concentration-Effect Correlation in the Rat with Adjuvant Arthritis

Aghazadeh‐Habashi

Kohan

Asghar

et al. 2014

Journal of Pharmaceutical Sciences

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Absorption and Bioavailability of Glucosamine in the Rat

Cited by 35 publications

References 34 publications

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

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

Pharmacokinetics of nebivolol in the rat: low oral absorption, loss in the gut and systemic stereoselectivity

Glucosamine Dose/Concentration-Effect Correlation in the Rat with Adjuvant Arthritis

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