Monitoring data that vary over time is an essential component of medical practice. This is doubly true in clinical trials in which the overall safety and efficacy of investigational treatments in populations must be monitored in addition to the status of the individual patients who receive them. We report the results of a randomized trial of four reporting methods for time-dependent information derived from clinical trials; narrative text, table, pie chart and icon. Multivariate analysis of variance with a repeated measures design was used to analyze the efficiency of subjects’ (physicians, research nurses and laboratory personnel) assimilation of information. Icons were found to be superior to the other reporting formats tested in both speed (p <0.0001) and accuracy (p = 0.02). The differences were most pronounced in subjects’ first exposure to the data, suggesting that icons reduce the time needed for training. We conclude that icons are a valuable method for presentation of time-dependent information in medical settings.

Twenty-seven patients with advanced malignancies were given 200 mg of ketoconazole orally every 6 or 12 h. Blood samples were collected during these intervals and after the last dose to determine plasma concentrations and half-lives. The mean plasma concentrations measured after the initial dose were 1.7 +/- 1.1 microgram/ml at 2 h, 0.9 +/- 0.2 microgram/ml at 6 h, and 0.7 +/- 0.4 microgram/ml at 8 h. Plasma concentrations rose significantly in patients on the every-6-h schedule. Concentrations were more variable in patients on the every-12-h schedule, and changes in mean plasma concentrations after 7 and 14 days were not significant. Half-lives ranged from 1.3 to 11.6 h in individual patients. The mean half-life for all patients studied was 3.7 +/- 0.6 h on day 1. The calculated area under the curve was 12.0 +/- 4.7 micrograms-h/ml on day 1; it increased after 7 and 14 days of administration (every-6-h schedule), suggesting plasma binding or wide drug distribution or both. Saturation of storage compartments is also suggested. Less than 1% of the administered dose was recoverable as active drug from the urine over 6 h.

No abstract

No abstract

Two metabolites of 2‐14C‐cyclocytidine (cyclo‐C) were found in the plasma and urine and a hydrolytic product, arabinosylcytosine (ara‐C), and its deaminated product, arabinosyluracil (ara‐U), were found in patients with cancer; 80% of the dose was found in urine in 24 hr, 70% as cyclo‐C and 10% as ara‐C and ara‐U. The plasma disappearance curve of ara‐C is curvilinear; the half‐life of ara‐C estimated from the terminal phase is 8 hr. By 6 hr, the ara‐C level is 0.35 µg/ml and falls exponentially to 0.06 µ/ml by 24 hr. Plasma concentration ratios of ara‐U to ara‐C are 0.1 to 0.3, 0.3 to 0.4, and 1.1 to 1.3 at 10 min, 1 hr, and 4 hr following intravenous injection of cyclo‐C at 200 mg/m2. Five min after an equal dose of ara‐C, this ratio is approximately 2, and by 4 hr, plasma ara‐C levels are immeasurable. After intramuscular and subcutaneous administration, cyclo‐C is rapidly absorbed. The plasma disappearance curves of the cyclo‐C hydrolytic product, ara‐C, are similar to those of the intravenous route. Intramuscularly, subcutaneously, and intravenously cyclo‐C should be equally effective. Intrathecal injections of cyclo‐C (50 mg/m2) result in an effective ara‐C level (0.1 µ/ml) in cerebrospinal fluid (CSF) at 24 hr. When cyclo‐C is given orally to fasting patients, less than 15% of the dose is excreted in urine in 24 hr and none can be detected in the plasma.