Dose - response relationship of bevacizumab in XXXX .

@entity1 @entity712 @entity7 @entity1353 @entity1415 @entity1884 @entity74
@entity1884 ( @entity1884 ), a @entity74 associated with @entity1415 and hepatic shunts, is responsible for high-output @entity712 in rare cases. Bevacizumab, which targets @entity7 , was shown to decrease both cardiac index (CI) and @entity1415 duration in @entity1884 @entity1 with severe liver involvement. The relationship between its serum concentration and change in both CI and @entity1415 duration was investigated to design the bevacizumab maintenance dosing regimen of future therapeutic studies. Twenty-five @entity1884 @entity1 with @entity1353 and high CI were included in a prospective non-comparative study. They received bevacizumab at a dose of 5  mg/kg per infusion every 14  days for a total of 6 injections. The relationships between bevacizumab serum concentration and both CI and @entity1415 duration were described using transit compartments and direct inhibition pharmacokinetic-pharmacodynamic models. The performances of different maintenance regimens were evaluated using simulation. Infusions every 3, 2 and one months were predicted to maintain 41%, 45% and 50% of @entity1 with CI <4 L/min/m(2) at 24 months, respectively. The fraction of @entity1 with <20  min @entity1415 per month was predicted to be 34%, 43% and 60%, with infusion every 3, 2 or one months, respectively. Simulations of the effects of different maintenance dosing regimens predict that monthly 5  mg/kg infusions of bevacizumab should allow sustained control of both cardiac index and @entity1415 .
