Mariko Morishita

Plasma catecholamine concentrations during a 72-hour aminophylline infusion in children with acute asthma

To explore the possibility that theophylline may act through adrenomedullary secretion of catecholamines, we examined the time courses of plasma norepinephrine (NE), epinephrine (E), and theophylline concentrations and peak expiratory flow (PEF) in nine children with an acute exacerbation of asthma receiving a 72-hour constant infusion of aminophylline. These measurements were made before (baseline) and at 2, 24, 48, and 72 hours after the infusion began. Plasma theophylline concentrations were kept constant in a near midpoint therapeutic range (mean +/- SEM, 14.1 +/- 1.3 to 16.1 +/- 1.1 micrograms/ml) during the 24- to 72-hour infusion periods. Compared with the respective baseline values (383.8 +/- 56.0 and 67.6 +/- 11.8 pg/ml for NE and E), the following postinfusion plasma catecholamines reached statistically significant difference: 664.0 +/- 125.1 pg/ml for NE at 24 hours (p less than 0.05), and 214.9 +/- 57.8, 233.7 +/- 82.2, and 137.6 +/- 39.4 pg/ml for E at 2, 24, and 48 hours (p less than 0.01). Despite the fact that similar plasma theophylline concentrations were maintained, plasma E, which peaked at 24 hours after dose, returned toward the baseline at the end of infusion (99.7 +/- 24.1 pg/ml), whereas this trend was not observed for NE. The postinfusion PEF increased (p less than 0.01) in a stepwise fashion, compared with the baseline, as the infusion progressed. The change in PEF correlated significantly (p less than 0.002) with plasma theophylline concentrations but not with the increase in plasma E from the baseline. Theophylline concentrations did not correlate with the increase in plasma NE or E from the baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled Drug Delivery Formulation with Safe Polymers

From the pharmaceutical point of view, the bioavailability, that is the amount and rate of absorption, is the most important factor determining the drug quality with respect to its efficacy and safety. Then, the bioavailability is controlled by well-designed dosage forms, for which interactions with surrounding components are applicable. Practically there are afforded various possibilities of modification of the interaction and then of control of drug delivery by a design of dosage forms, using polymers. The present talk will contain, as example, enteral delivery of insulin by Eudragit microsphere with protease inhibitors, topical mucosal drug delivery systems with adhesive polymers, and nasal delivery of salmon calcitonin by functional powder preparations using microcystalline cellulose. These polymers are guaranteed already as pharmaceutically safe ones.