Effect of local XXXX of the bladder on @entity1138 pharmacokinetics during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma.

@entity1 @entity137 @entity5 @entity1138 @entity1139 @entity150 @entity221
AIMS: To assess the effect of local @entity221 on the systemic absorption of @entity1138 ( @entity1139 ) during intravesical chemotherapy for the treatment of superficial transitional cell @entity150 , and to establish the likely safety of this procedure. METHODS: Group 1 (n = 12) received 20 mg intravesical @entity1139 plus local @entity221 , group 2 (n = 13) 20 mg @entity1139 alone, group 3 (n = 16) 40 mg @entity1139 plus local @entity221 and group 4 (n = 10) 40 mg @entity1139 alone. @entity1 in groups 1, 2, and 4 underwent post- @entity5 resection adjuvant treatment, whereas those in group 3 still had @entity5 present and were treated to eradicate it. Intravesical instillation lasted 60 min, with the solution (50 ml) being replaced after the first 30 min. Blood samples were taken before, and every 15 min during instillation. @entity1139 concentrations in plasma and in urine were determined by h.p.l.c. RESULTS: The highest @entity1139 plasma concentration (67.9 ng ml(-1)) occurred in a @entity1 in group 3. This value was well below the threshold concentration (400 ng ml-1) for myelosuppression. Local @entity221 associated with the intravesical chemotherapy enhanced plasma @entity1139 concentrations at 30, 45 and 60 min compared with chemotherapy alone (Group 1 vs 2, P < or = 0.008). Systemic exposure to @entity1139 was not significantly increased by doubling the intravesical dose when intravesical chemotherapy alone was administered. @entity1 in group 3 displayed the highest degree of @entity1139 absorption and the greatest variability in pharmacokinetics between @entity1 . CONCLUSIONS: Local @entity221 enhances the systemic absorption of @entity1139 during intravesical chemotherapy for @entity150 . In the doses used, plasma @entity1139 concentrations were always more than six times lower than those shown to cause @entity137 .
