The objectives of these studies were to determine the amount and distribution of the aminoglycoside antibiotic amikacin delivered to rabbit eyes following transscleral iontophoresis and to determine the inter-study reproducibility of delivery over three identical studies. New Zealand White rabbits (N = 6 per dose group) were treated with a 200-mg/mL amikacin solution at 0, 2, 3 or 4 mA of (+) DC current for 20 minutes. Amikacin concentrations in eye tissues were highest with the 4-mA treatment. Concentrations for all three studies at this current were approximately 5.4, 40, 41, 343, and 92 mcg/g in the vitreous humor, anterior segment, non-treated hemisphere of the sclera, treated hemisphere of the sclera, and retina/choroid, respectively. These values were approximately 27, 50, 40, 10, and 13 fold greater than in the 0-mA control group and are well above the in vitro minimum inhibitory concentrations (MICs) for this drug. Inter-study reproducibility (measured as %CV) depended on the tissue type and treatment group and ranged from 8% for the retina/choroid to 51% for the anterior segment in the 4-mA group. Pretreatment with topical proparacaine hydrochloride local anesthetic did not affect amikacin delivery and total drug delivered was not affected by delivery time for the same total charge administered. Therapeutically relevant amounts of amikacin were delivered into eye tissues in a reproducible and controllable manner.
The purpose of this study was to evaluate the effect of 1 hour of everyday exercise (walking at patient's own pace) on serum digoxin concentrations. Nine white male subjects (ages 58-74) who had been taking the same digoxin dose for greater than 1 month participated. There were three continuous phases: 1 hour of rest, 1 hour of exercise, and a final hour of rest. Serum digoxin concentrations were drawn every 20 minutes. During the first rest period, serum digoxin concentrations rose 30% from the first concentration drawn in the study. After 1 hour of exercise, serum digoxin concentrations fell 26.8% from the last concentration of the first rest period. At the end of the second hour of rest, serum digoxin concentrations increased by 36.6% from the last concentration. Repeated measures analysis of variance demonstrated a significant (P less than .01) change in serum digoxin concentrations. Significant (P less than .01) differences were found between sampling times 0 and 60, 60 and 80, 60 and 100, 60 and 120 and 180 minutes using a paired t-test with Bonferroni correction. A weak correlation (r = 0.74, r2 = 0.55) between percent change in concentrations and age during the exercise phase was found, but there was no correlation between the percent change in concentrations and age during the two immobilization phases. Because significant changes in concentrations occurred during each phase of the study, we conclude that the influence of everyday exercise should be taken into account when interpreting serum digoxin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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