We have described the influence of weight, renal function, age and plasma protein binding on the pharmacokinetics of linezolid. This combined pharmacokinetic, pharmacodynamic and turnover model identified that the most common mechanism of thrombocytopenia associated with linezolid is PDI. Impaired RF increases thrombocytopenia by a pharmacokinetic mechanism. The linezolid dose should be reduced in RF.
Using the urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration, effects of participation in a two-day ultramarathon race period on oxidative DNA damage were investigated in Japanese nonprofessional runners. Before the first day (baseline), after the first day (mid-race) of 40-km running, and after the second day (post-race) of 90 km running, biomaterials were successfully sampled from 95 participants (males, 79; females, 16) who completed the full race. We analyzed urine for 8-OHdG and blood for aspartate aminotransferase (AST), creatine phosphokinase (CPK) and myoglobin, and evaluated fluctuation in the values at three sampling time points. Adjusted baseline urinary 8-OHdG levels (microg/g creatinine) (mean +/- standard deviation) showed no significant differences between males and females, at 2.85 +/- 1.17 and 3.04 +/- 1.56, respectively. In males, mid-race urinary 8-OHdG levels rose to 3.29 +/- 1.15 (p < 0.01), but then returned to 2.73 +/- 1.16 at the post-race time point (p < 0.01). In females, a similar increase to 3.32 +/- 1.47 and subsequent decline to 2.80 +/- 1.47 were noted. In contrast, AST, CPK and myoglobin were increased at both mid- and post-time points and particularly the latter, independent of the sex. Extreme prolonged exercise in a two-day ultramarathon race period causes oxidative DNA damage but antioxidant repair systems are apparently induced to protect against oxidative DNA stress with physical exercise.
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