Participants in marathon races may require medical attention and the performance of laboratory assays. We report the changes in basic biochemical parameters, cardiac markers, CBC counts, and WBC differentials observed in participants in a marathon before, within 4 hours, and 24 hours after a race. The concentrations of glucose, total protein, albumin, uric acid, calcium, phosphorus, serum urea nitrogen, creatinine, bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total creatine kinase, creatine kinase-MB, myoglobin, and the anion gap were increased after the race, consistent with the effects of exertional rhabdomyolysis and hemolysis. The increase in WBC counts was due mainly to neutrophilia and monocytosis, with a relative decrease in circulating lymphocytes, consistent with an inflammatory reaction to tissue injury. A significant percentage of laboratory results were outside the standard reference ranges, indicating that modified reference ranges derivedfrom marathon runners might be more appropriatefor this population. We provide a table of modified reference ranges (or expected ranges) for basic biochemical, cardiac, and hematologic laboratory parameters for marathon runners.

These findings suggest that there are elevated levels of oxidative stress and glutamatergic neurotransmission in tardive dyskinesia, both of which may be relevant to the pathophysiology of tardive dyskinesia.

Clozapine (CLZ) and its metabolites norclozapine (NOR)and clozapine-N-oxide (NOX) were assayed in rat serum and brain tissue after intraperitoneal injection of CLZ. Clozapine levels rose with dose, averaging 28 ng/ml (87 nmollL) serum per milligram/kilogram dose. Brain-and serum-CLZ levels correlated closely, averaging 24-fold higher in brain. Norclozapine and NOX averaged approximately 58% and 13% of CLZ in serum, respectively, whereas in brain, NOR was detected only at KEY WORDS: Clozapine; Clozapine-N-oxide; Drug assay; F1uoxetine; Liquid chromatography; Norclozapine; Photodiode-array; Spectrophotometry; Valproic acid Despite its invention in 1960 and its clinicdl use for more than two decades, information on the disposi tion and metabolism of the atypical antipsychotic drug clozapine (CLZ) remains limited, and guidelines for cli nical application and interpretation of plasma as says of CLZ or its metabolites are not well established (Baldessarini and Frankenburg 1991). Several clinical studies of circulating concentrations of CLZ and its prominent metabolites norclozapine (NOR) and cloz apine-N-oxide (NOX) using contemporary analytical methods have been reported and were reviewed re cently by Volpicelli and colleagues (1993 doses greater than or equal to 10 mg/kg (approximately 5.6% of CLZ) and NOX was undetectable. Levels peaked within 30 minutes, and elimination of CLZ from brain and CLZ or NOR from blood was very rapid (half-life = 1.5 to 1.6 hours). A week of daily dosing with CLZ led to no accumulation of drug in brain; a week of fiuoxetine pretreatment increased analyte concentrations (serum, 86%; brain, 61%), but valproate had little effect. [Neuropsychopharmacology 9:117-124, 1993] dicate that serum concentrations of CLZ have ranged from 60 to 600 ng/ml at about 12 hours after daily clini cal doses of CLZ of 100 to 500 mg. Circulating levels of the metabolite NOR in man often approach those of CLZ itself (averaging approximately 75% to 90%, but ranging widely (from approximately 10% to over 100%), whereas concentrations of NOX have been consistently lower (typically, 10% to 35% of CLZ). There are recent indications that CLZ may interact with other agents in man, with decreases in circulating concentrations associated with smoking (Haring et al. 1990) and treatment with phenytoin , and increases associated with cimetidine (Szy manski et al. 1991) and fluoxetine (Centorrino et al. 1993b), whereas valproate appears to have lesser effects (Centorrino et al. 1993b). Clozapine levels also rise predictably with dose (Kane et al. 1981;Haring et al. 1990; Centorrino et al. 1933a) and with age (Haring et al. 1990) and tend to be slightly higher in women, even on a dose-and-weight-corrected basis to account for typically higher milligram/kilogram doses in men (Haring et al. 1990;Centorrino et al. 1993a).