RESUMEN
We investigated changes in drug disposition and toxicities with CPT-11 in 15 dialysis patients with gastrointestinal cancers to clarify whether CPT-11 could be administered safely in such patients. For comparison, the same parameters were also investigated in 10 cancer patients not undergoing dialysis. Items investigated included (1) plasma concentrations of SN-38, SN-38G and CPT-11 at 0, 1, 12, 24, 36, 48 and 72 h after administration, together with a comparison of mean AUC values for 3 dose levels of CPT-11 (50, 60 and 70 mg/m2) in dialysis patients and controls; and (2) occurrence of adverse events. Several findings emerged from this study: (1) No significant difference was observed in the AUC for SN-38 or CPT-11 between the dialysis and control groups; (2) The AUC for SN-38G at each dose was significantly higher in dialysis patients; and (3) Grade 1-4 leucopenia was observed in 11 of the dialysis patients. One patient developed grade 4 leucopenia and died due to sepsis. Anorexia, diarrhea, nausea, alopecia and interstitial pneumonia occurred in 6 dialysis patients. We found changes in drug dispositions of CPT-11, SN-38 and SN-38G in dialysis patients, suggesting that hepatic excretion, especially that of SN-38G, was increased. No significant difference in occurrence of adverse events was observed between the 2 groups. This indicates that CPT-11 can be administered safely in patients on dialysis.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Gastrointestinales/complicaciones , Neoplasias Gastrointestinales/tratamiento farmacológico , Diálisis Renal , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/sangre , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/sangre , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/tratamiento farmacológico , Femenino , Humanos , Irinotecán , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Neoplasias del Recto/complicaciones , Neoplasias del Recto/tratamiento farmacológico , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
BACKGROUND: This study evaluated the usefulness of machine perfusion preservation parameters as indicators of kidney graft viability. METHODS: Eighty-eight cadaveric kidneys were analyzed in this study. Of these, 74 kidneys (84.1%) were procured from nonheartbeating donors. The criteria for an acceptable kidney for transplantation were a perfusion flow of more than 0.4 mL/min/g with a concurrent decreasing perfusion pressure. The average perfusion pressure was 30-50 mmHg. We divided the kidneys into three groups: group 1 (n=35), 0.45-0.65 mL/min/g machine perfusion flow (MPF); group 2 (n=30), 0.65-0.90 mL/min/g MPF; and group 3 (n=23), more than 0.9 mL/min/g MPF. RESULTS: A higher rate of primary nonfunction (PNF; 25.7%) was found in group 1, compared with 6.7% in group 2 and 0% in group 3. A higher rate of 30.4% immediate function was found in group 3, compared with 16.7% in group and 8.6% in group 1. However, a longer period of acute tubular necrosis (ATN; 12.0 days) was found in group 1 compared with 8.6 days in group 2 and 8.7 days in group 3. PNF was detected in 7 (77.8%) cases with more than 16 hr of total ischemic time (TIT) in group 1. In contrast, all of nine cases with more than 16 hr of TIT in group 3 were functional. CONCLUSIONS: MPF is a reliable indicator of graft viability based on the rate of PNF and immediate renal allograft function, especially in marginal donors.
