Relationship between clinical severity of "new" bronchopulmonary dysplasia and HRCT abnormalities in VLBW infants.

BACKGROUND: To assess the relationship between HRCT abnormalities and the clinical severity of "new" bronchopulmonary dysplasia (BPD) and respiratory assistance in <1500 g preterm infants. METHODS: HRCT was performed at the time of discharge in 109 preterm infants with BPD who were born between 2008 and 2014. BPD severity was defined as mild, moderate, or severe according to the NIH diagnostic criteria. Total HRCT scores for each infant were obtained from the sum of the number of BPD lobes assessed by two radiologists: a hyperaeration score (Hs) composed of decreased attenuation, mosaic attenuation, and bulla/bleb, and a parenchyma score (Ps) composed of linear lesions, consolidation, bronchial wall thickening, and bronchiectasis. We compared HRCT scores based on BPD severity and respiratory modes, such as invasive mechanical ventilation (IMV), non-invasive MV (NIMV), and oxygen therapy. RESULTS: Among the group of included infants (n = 101), mild BPD was found in 46.5%, moderate BPD in 45.5%, and severe BPD in 7.9%. When partial correlation was adjusted by gestational age (GA) and birth weight, the duration of NIMV was correlated with Ps (r = 0.382, P < 0.001), Hs (r = 0.223, P = 0.027), and total score (r = 0.384, P < 0.001). The duration of oxygen therapy was correlated with Ps (r = 0.374, P < 0.001) and Hs (r = 0.227, P = 0.023). Ps showed a correlation with BPD severity (r = 0.381, P = 0.007) in infants born at ≤26 weeks (GA) and those born at >27 weeks GA (r = 0.298, P = 0.042). CONCLUSIONS: Parenchymal changes showed a greater correlation with the clinical severity of "new" BPD cases, especially in infants born at ≤26 weeks GA. The use of NIMV showed a greater correlation with Ps than Hs.

Mechanism of enhanced bioavailability and diuretic effect of azosemide by ascorbic acid in rats.

To increase the extent of comparative oral bioavailability (F) value and the diuretic and natriuretic effects of orally administered azosemide, ascorbic acid was coadministered to rats. The rationales for this study are that ascorbic acid might inhibit intestinal first-pass effect of azosemide and might increase the unionized fraction of azosemide at the receptor sites. After oral administration of azosemide (20 mg/kg) with 100 mg of ascorbic acid, the F value (138% vs. 100%), 8-h urinary excretion of azosemide (5.18% vs. 1.32% of oral dose), 8-h urine output (41.3 vs. 23.0 ml), and 8-h urinary excretion of sodium (24.6 vs. 15.3 mmol/kg) were greater than controls (without ascorbic acid). The amount of spiked azosemide remaining after 30 min incubation of 50 mug of azosemide with the 9000 g supernatant fraction of rat small intestine was significantly greater by 100 microg of ascorbic acid (45.3 vs. 40.9 microg) than controls (without ascorbic acid). After oral administration of azosemide with NH4Cl, the urine pH decreased by 0.5 U, and 8-h urine output (25.8 vs. 11.0 ml) and 8-h urinary excretion of sodium (13.3 vs. 6.89 mmol/kg) were significantly greater than controls (without NH4Cl). The increase in F value and diuretic and natriuretic effects of azosemide with coadministration of ascorbic acid seemed to be due to reduced intestinal first-pass metabolism of azosemide, increased urinary excretion of azosemide, and increased unionized fraction of azosemide at the renal tubular receptor sites.

Dose-dependent pharmacokinetics of itraconazole after intravenous or oral administration to rats: intestinal first-pass effect.

The dose-dependent pharmacokinetics of itraconazole after intravenous (10, 20, or 30 mg/kg) and oral (10, 30, or 50 mg/kg) administration and the first-pass effects of itraconazole after intravenous, intraportal, intragastric, and intraduodenal administration at a dose of 10 mg/kg were evaluated in rats. After intravenous administration at a dose of 30 mg/kg, the area under the plasma concentration-time curve from time zero to infinity (AUC(0- infinity )) was significantly greater than those at 10 and 20 mg/kg (1,090, 1,270, and 1,760 micro g. min/ml for 10, 20, and 30 mg/kg, dose-normalized at 10 mg/kg). After oral administration, the AUC(0- infinity ) was significantly different for three oral doses (380, 687, and 934 micro g. min/ml for 10, 30, and 50 mg/kg, respectively, dose-normalized at 10 mg/kg). The extent of absolute oral bioavailability (F) was 34.9% after an oral dose at 10 mg/kg. The AUC(0- infinity ) (or AUC(0-8 h)) values were comparable between intravenous and intraportal administration and between intragastric and intraduodenal administration, suggesting that the hepatic and gastric first-pass effects were almost negligible in rats. However, the AUC(0-8 h) values after intraduodenal and intragastric administration were significantly smaller than that after intraportal administration, approximately 30%, suggesting that the intestinal first-pass effect was approximately 70% of that of an oral dose of 10 mg/kg. The low F after oral administration of itraconazole at a dose of 10 mg/kg could be mainly due to the considerable intestinal first-pass effect.