Abstract Background: Eri & Cap are active as single agents in metastatic breast cancer, but the combination appears particularly active & well tolerated clinically. We explored the hypothesis that normalisation of tumor vasculature by Eri seen in preclinical models may enhance delivery of Cap to the tumor when given in combination. Methods: Mice bearing MDA-MD-231 xenografts were treated with Cap 540mg/kg p.o. day 1 alone or following Eri 1mg/kg i.v. on day -8 then sacrificed on day 1 at 15min, 30min, 1h, 2h, 4h, 6h or 24h after Cap (n=3/ time point). Concentrations of Cap & its metabolites (5'-deoxy-5-fluorocytidine, 5DFCR; 5-Fluoro-5'-deoxyuridine, 5DFUR; 5-Fluorouracil, 5FU; 5-Fluorouridine, 5FUrd; & 5-Fluoro-2'-deoxyuridine, 5FdUrd) in plasma, tumor, skin & muscle were analysed by LC-MS/MS. Half the tumor was reserved to study Cap distribution using matrix-assisted laser desorption/ionization mass spectrometry imaging with haem imaged as a surrogate marker for tumour vasculature. Results: We found no differences in the plasma, skin, muscle or tumor PK profiles of Cape & its metabolites with the addition of Eri (Table 1). In both treatment arms intratumoral concentrations of 5DFUR, 5FU, 5FUrd & 5FdUrd appeared higher in tumors while those of Cape & 5DFCR appeared higher in normal healthy tissues. To mitigate the variability in tumor Cape concentrations between animals, we also expressed the results as the ratio of drug concentration in tumour:healthy tissue but again found no apparent effect of Eri on intratumoral drug concentrations. Analyses of drug distribution are on-going & will be presented. Conclusion: No clear effect of Eri on intratumoral concentrations of Cape or its metabolites was seen. We are exploring potential differences in tumour drug distribution. Citation Format: Maria Jove Casulleras, Jade Spencer, Paul Loadman, Malcolm Clench, Steve Shnyder, Patricia Cooper, Cristina Russo, Amanda Race, Ramon Salazar, Chris Twelves. Preclinical intratumoral pharmacokinetics (PK) of capecitabine (Cap) given +/- eribulin (Eri) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4926.