Abstract A finite element model is developed to predict the penetration time-history of three different solutes into the human lumbar disc following intravenous injection. Antibiotics are routinely administered intravenously in spinal surgery to prevent disc infection. Successful prophylaxis requires antibiotics to reach adequate inhibitory levels. Here, the transient diffusion of cephazolin is investigated over 10h post-injection in a human disc model subject to reported concentrations in the blood stream as the prescribed boundary sources. Post-injection variation of cephazolin concentrations in the disc adjacent to supply sources closely followed the decay curve in the blood stream and fell sharply with time. Much lower concentrations were computed in the inner annulus and nucleus; much of the disc (80% at 1h and 49% at 4h) experienced concentrations below required inhibitory level of 1mg/L in agreement with measurements. Changes in endplate permeability, disc size, and solute molecular weight had profound effects on concentration profiles at all times and regions, especially in the disc centre, demonstrating their crucial roles on the adequate delivery of drugs. Larger solutes markedly slow transport into the disc. The failure to reach critical therapeutic levels in the central disc regions, especially when endplates calcify and in larger discs, raises concerns and calls for caution in attempts to extrapolate findings of studies on animals with much smaller and non degenerate discs to the human discs. The current study also demonstrates the capability of computational models in predicting the transport of intravenously injected solutes into the disc.