Altered XXXX pharmacokinetics during the perioperative period.

@entity1 @entity801 @entity5 @entity954
The effect of surgery on the pharmacokinetics of @entity801 in hospitalized @entity1 was studied. @entity1 with @entity5 undergoing surgery of the head and neck were given @entity801 in doses calculated to achieve peak serum concentrations of 6-8 micrograms/mL and trough concentrations of 1-2 micrograms/mL. Each @entity1 received a loading dose at the time of @entity954 , followed by five maintenance doses at eight-hour intervals. Steady-state peak and trough serum @entity801 concentrations were predicted using a one-compartment open pharmacokinetic model and literature values for volume of distribution (V) and first-order elimination rate constant (k). Serum @entity801 concentrations were measured 0.25 hours before and at 0.5, 3.5, and 6.5 hours after completion of infusion of the second maintenance dose. Peak and trough serum concentrations were obtained by extrapolation from these measured concentrations using weighted, nonlinear least squares regression. Predicted versus measured serum @entity801 concentrations and estimated versus observed values for V and k were compared. Eight @entity1 and seven @entity1 had evaluable serum @entity801 concentrations. @entity1 received a mean calculated maintenance dose of 4.4 +/- 0.7 mg/kg/day. Mean extrapolated peak and trough serum @entity801 concentrations were significantly lower than predicted, and observed values of V and k were significantly greater than estimated values. @entity801 dosages calculated using standard pharmacokinetic variable values may not produce therapeutic concentrations in @entity1 undergoing surgery. Monitoring of serum concentrations with dosage adjustment when indicated is necessary for optimal therapy in these @entity1 .
