Renal clearance of @entity1499 in XXXX during high-dose oral and intravenous infusion therapy.

@entity4181 @entity1 @entity8 @entity1500 @entity1011 @entity1499
The @entity8 and clearance of @entity1499 ( @entity1500 ) following high-dose (800 mg) therapy followed by @entity4181 rescue was studied in 12 @entity1 (2 female, 10 male): the mean age was 49.3 +/- 5.5 (SE), weight 68.6 +/- 3.9 (SE) and body surface area 1.8 +/- 0.1 m2. Plasma and urine were collected over 154 h at intervals of 2-24 h, and the collection times, volume, and pH of urine samples recorded. Total @entity1500 concentrations in urine and plasma were measured by the highly specific competitive protein-binding assay method. Plasma and urinary @entity1011 levels were measured on an SMA-12 autoanalyser. The renal clearance of @entity1500 was calculated for each urine collection period. Following oral administration, clearance values during the first 6 h were high at 257 +/- 8.3 (ml/Min), followed by a trough in clearance of 27.9 +/- 4.2 (ml/min) in the 20- to 30-h period. This was followed by a secondary rise of @entity1500 renal clearance to 180.4 +/- 14.6 ml/min during the 68- to 84-h period and again to 84.9 +/- 17.1 ml/min between 84 and 112 h. In the last two periods it rose to 209 +/- 57.9 ml/min. Similar fluctuations were seen following IV administration. The changes in clearance were statistically significant at the p less than 0.005 level. It is suggested that high concentrations of @entity1500 in the renal tubules result in inhibition of carrier protein synthesis, leading to a fall in active tubular secretion. When @entity1500 concentrations fall the tubular cell recovers and a secondary rise in renal clearance occurs, leading to cyclical changes in @entity1500 elimination.
