The incomplete recovery of TRA (~76%) is probably a result of the long t½ of TRA (197 hours) and is not uncommon for an alkylating agent [21]. Measurable levels of TRA were still present in the last urine and fecal samples, even in those collected 3 weeks after the 14C-bendamustine infusion, suggesting that higher recovery could have been obtained if the collection time had been further extended. However, the added value of additional excretion data was, in this case, considered limited and did not outweigh the accompanying Androgen Receptor pathway Antagonists additional burden for the patients. Urinary excretion of 14C-bendamustine–derived radioactivity

(49% of the administered dose) was more predominant than fecal excretion (27%). The urinary to fecal excretion ratio differed slightly from the ratio in rats, where ~49% of the administered dose was recovered in feces, with total recovery of ~90% [14]. Consistent with the rapid CL of bendamustine, M3, and M4 from plasma, these compounds were predominantly

found in the 0- to 2-hour urine samples. Additionally, their relative amounts in urine were qualitatively the same as in Selleckchem Tubastatin A plasma (i.e., amount of bendamustine > amount of M3 > amount of M4). In contrast, although HP2 concentrations in plasma were substantially lower than the bendamustine concentrations, the amount of HP2 recovered in urine was comparable to the recovered amount of CX-6258 chemical structure bendamustine, indicating that hydrolysis of bendamustine facilitates renal excretion. The continuing recovery of small amounts of HP2 in urine correlates with the continuing low levels of HP2 that were measured in plasma. The first 24-hour urine recovery Decitabine purchase values of unchanged bendamustine (3.31 ± 1.95%), M3 (0.73 ± 0.37%), M4 (0.08 ± 0.11%), and HP2 (4.89 ± 2.91%), adding up to a total of 9.01 ± 1.99%, are comparable to values seen in previous studies. Teichert and colleagues [13] recovered 3.23 ± 3.69%, 0.30 ± 0.31%, 0.05 ± 0.03%, and 0.94 ± 0.13% of the administered dose as bendamustine, M3, M4, and HP2, respectively, in the 0- to

24-hour urine samples after bendamustine infusion. In two studies, Rasschaert and colleagues recovered 8.3% (range 2.7–26.0%) [15] and 9.8% [16] of the administered dose in the first micturition after a bendamustine infusion as bendamustine, M3, M4, HP1, and HP2 combined. In the present study, extensive measures were applied to minimize degradation of bendamustine. Each urine void was processed individually and immediately; urine was diluted in prechilled control human plasma for stabilization and immediately stored at −70 °C pending bioanalysis, when samples were thawed in ice water and kept in ice water whenever possible during sample preparation. The stability of bendamustine was confirmed under these conditions [17]. Still, considerable variation was present in the urinary recovery of bendamustine.