Pharmacokinetics and pharmacodynamic effects of aqueous @entity3988 in healthy XXXX .

@entity3988 @entity1 @entity713 @entity1671
Aqueous @entity3988 was given to ten healthy male volunteers in a single oral dose of 2.5 mg/kg body weight. Serum @entity3988 levels were measured at various intervals up to 24 hours after administration of the drug as were blood pressure, heart rate, and PR interval. The pharmacokinetics followed a one-compartment model in six and two-compartment model in four subjects. The mean distribution half-life in the latter four subjects was 15.8 +/- 3.7 minutes (range, 10.4-18.8 min). In the ten subjects, the peak serum @entity3988 level was attained in 20 to 45 minutes (mean, 32.5 +/- 9.5 min) and ranged from 136 to 701 ng/mL (mean, 332 +/- 180 ng/mL). The elimination half-life ranged from 2.8 to 4.8 hours (mean, 3.8 +/- 0.6 hr). The area under the concentration-time curve varied from 508 to 2,245 ng-hr/mL, indicating differing bioavailability. Slight but significant blood pressure reduction was seen only at one to three hours. Changes in heart rate were not significant at any measurement. Transient @entity1671 , beginning at ten to 20 minutes after administration, was noted in nine subjects, reflecting the vasodilatory effect of the drug. Significant prolongation (greater than 10%) of PR intervals began at ten minutes in three, at 20 minutes in six, and at 30 minutes in one @entity1 , and progressed to second-degree Wenckebach @entity713 in six subjects 20 to 60 minutes after administration and third-degree @entity713 in one @entity1 45 minutes after dosing. These @entity713 resolved by the third hour without treatment, and PR prolongation resolved by the fifth to seventh hours.(ABSTRACT TRUNCATED AT 250 WORDS)
