Locomotor activity and body temperature in selected mouse lines differing greatly in feed intake.

Locomotor activity, body temperature, feed intake, and BW were measured on 382 mature male mice sampled from lines previously selected (25 generations) for either high (MH) or low (ML) heat loss and an unselected control (MC). Animals were from all 3 independent replicates of the 3 lines and across 4 generations (68 through 71). Locomotor activity and body temperatures were obtained using implanted transmitters with data collection over 4 d following a 3-d postsurgery recovery period. Data were collected every minute and then averaged into 30-min periods, thus providing 192 data points for each mouse. Least-squares means for feed intake adjusted for BW (Feed/BW, feed·BW(-1)·d(-1), g/g) were 0.1586, 0.1234, and 0.1125 (±0.0022) for MH, MC, and ML, respectively, with line being a highly significant source of variation (P < 0.0003). Line effects for locomotor activity counts, transformed to the 0.25 power for analysis, were significantly different, with MH mice being 2.1 times more active than ML mice (P < 0.003); MC mice were intermediate. Differences in body temperature were significant for both line (P < 0.03) and day effects (P < 0.001), with a 0.32°C difference between the MH and ML lines. Fourier series analysis used the combined significant periodicities of 24, 18, 12, 9, 6, and 3 h to describe circadian cycles for activity and body temperature. All 3 lines expressed daily peaks in body temperature and locomotor activity ∼3 h into darkness and ∼2 h after lights were turned on. There was a stronger relationship between locomotor activity and Feed/BW (P < 0.0001) than between body temperature and Feed/BW (P < 0.01); differences between lines in locomotor activity and body temperature explained 17% and 3%, respectively, of differences between lines in Feed/BW. Thus, line differences in locomotor activity contribute to line differences in maintenance, but approximately 80% of the differences between the MH and ML selection lines in Feed/BW remains independent of differences in locomotor activity.

Multiple-dose pharmacokinetics and safety of rufloxacin in normal volunteers.

The pharmacokinetics and safety of rufloxacin were evaluated in a double-blind, placebo-controlled study. Two groups of 16 healthy volunteers were given a single oral loading dose of 400 or 600 mg of rufloxacin on day 1 of the study. A single daily maintenance dose of 200 or 300 mg was then administered for a further 9 days; in addition, four subjects in each group received placebos. Rufloxacin levels in plasma and urine were determined by high-performance liquid chromatography. Following the initial dose, the mean (+/- standard error of the mean) peak concentrations of rufloxacin in plasma were 3.35 +/- 0.12 micrograms/ml in the 400-mg group and 4.54 +/- 0.19 micrograms/ml in the 600-mg group. They were generally reached 2 to 3 h after dosing. At the end of treatment, maximum levels in plasma rose to 4.51 +/- 0.15 and 7.20 +/- 0.25 micrograms/ml in the 400-mg and 600-mg groups, with a mean extent of accumulation (fold) of 3.1 +/- 0.1 and 3.3 +/- 0.1. For the 400-mg and 600-mg groups, the elimination half-lives were 40.0 +/- 1.5 and 44.0 +/- 1.3 h, mean residence times were 57.8 +/- 2.2 and 63.7 +/- 1.8 h, apparent volumes of distribution were 132 +/- 4 and 139 +/- 5 liters, and apparent total body clearance were 39 +/- 1 and 44 +/- 4 ml/min, assuming complete bioavailability. Of the total dose administered, the percentages excreted in urine were 49.6 +/- 1.3 and 51.1 +/-2.1%, with renal clearances of 21 +/- 1 and 22 +/- 2 ml/min, for the 400-mg and 600-mg groups. On the whole, the treatments were well tolerated, but some minor adverse events (mainly headache, insomnia, or abdominal discomfort) were reported for 7 subjects on abnormalities were detected in the laboratory examinations or in ocular function tests. This study shows that a 200-mg daily oral dose of rufloxacin preceded by a loading dose of 400 mg are well tolerated and produce steady-state concentrations in plasma above the MIC for most susceptible pathogens.