Figure 3.

Plasma and tissue concentration time course. Concentrations based on the quantitation of radioactivity are expressed as μg of oligonucleotide equivalents/ml or g (mean ± SD) after oral administration of ³⁵S-labeled Oligo AS (10 mg/kg) into mice bearing LS174T xenografts (three mice for each time point). To illustrate the relative levels of Oligo AS in tumor and plasma compared with other tissues, the data on tumor and plasma were plotted in both A and B. Pharmacokinetic parameters are summarized in Table 2; data indicate a significant accumulation and retention of the MBO in tumor tissues. Oligo AS-derived radioactivities also were detected in other host tissues (A–C) with a similar pattern seen in a previous study with a same type of MBO (27). Significant urinary excretion of Oligo AS-derived radioactivity was observed (D). Based on radioactivity, the MBO had a good oral bioavailability (>48% in 48 h after dosing).