XXXX absorption and disposition: effect of surgical procedures for @entity10189 .

@entity1 @entity10189 @entity6842 @entity13136
This study was designed to determine whether the surgical procedures for @entity10189 influence @entity13136 ( @entity6842 ) absorption and disposition. Prior to and on the average 79 days after surgery, eight @entity1 received 10 mg kg-1 of @entity13136 orally. Blood samples were obtained at regular intervals over 24 h and urine was collected for 48 h. Vagotomy with pyloroplasty or with gastrojejunostomy had no effect on @entity6842 kinetics. Vagotomy with partial gastrectomy decreased the @entity6842 plasma peak concentrations from 43.9 +/- 7.1 (mean +/- SEM) to 17.2 +/- 5.2 micrograms ml-1 (p less than 0.05) and increased the time required to reach this peak from 2.6 +/- 0.8 to 9.8 +/- 2.8 h (p less than 0.05). @entity6842 rate constant of absorption decreased only slightly (1.22 +/- 0.45 to 0.24 +/- 0.07 h-1) and @entity6842 bioavailability was not affected at all. In two (out of four) @entity1 , @entity6842 volume of distribution and total body clearance increased, as reflected in the 41 per cent decrease in the mean area under the @entity6842 plasma concentration-time curve. No changes were detected in @entity6842 protein binding. Computer simulations indicated that in some subjects @entity6842 plasma concentrations at steady state could be 76 per cent lower following vagotomy with partial gastrectomy than before surgery. It was concluded that vagotomy and antrectomy with a gastroduodenostomy or Billroth I reconstruction decreased the rate of @entity6842 absorption and only in some subjects increased the @entity6842 volume of distribution and rate of elimination. The possible mechanisms involved in these reported kinetic changes are discussed.
