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

摘要

PurposeTests 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.MethodsHere, 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.ResultsHuge 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.ConclusionsChanges 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...