Disease relevance of Area Under Curve

• Neutropenia was dose limiting at the carboplatin target AUC of 12 mg.min/mL [1].
• Severity of coronary atherosclerosis correlated significantly (P < .05 to P < .01) with basal proinsulin (r = .40) and the proinsulin area under the curve (AUC) (r = .34), basal insulin (r = .31), basal C peptide (r = .30), and the glucose AUC (r = .30) [2].
• High peak concentrations of immunotoxin in the serum, a long T1/2, and large areas under the curve (AUC) correlated with both clinical response and toxicity [3].
• In an attempt to improve outcomes for patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT), we conducted a phase 1/2 study in which targeted irradiation delivered by 131I-anti-CD45 antibody was combined with targeted busulfan (BU; area-under-curve, 600-900 ng/mL) and cyclophosphamide (CY; 120 mg/kg) [4].
• Carboplatin dosing by the area under the curve (AUC) may minimize thrombocytopenia [5].

Psychiatry related information on Area Under Curve

• RESULTS: Protocol 1: In the absence of esophageal acid, ketamine had no effect on either esophageal or foot pain thresholds (area-under-the-curve, [AUC] P = 0.36 esophagus, P = 0.34 foot, ANOVA) within 30 minutes of cessation of the infusion [6].
• Airway response was measured by FEV1, and the EAR (0-3 h) and LAR (3-10 h) were expressed as corresponding areas under the time-response curves (AUC) [7].
• 2. Multiple regression models showed that neuropsychological tests accounted for 23% of the variance associated with S-100 AUC release, after partialing out the effects of age and bypass time [8].
• Correlations between the measure of social dominance and aggregated AUC cortisol stress responses rose from r = -.47 on day two of the experimental session to r = -.70 after aggregating days two to five [9].
• Since novelty is a random situational factor likely to mask individual differences in the stress response, the AUC cortisol stress responses of days two to five were consecutively aggregated, excluding the first day [9].

High impact information on Area Under Curve

• When compared with the control group, the change in testosterone AUC was significant for the 300-mg/d group (P<.001) but not for the 100-mg/d group (P = .48) [10].
• RESULTS: Patients treated with metformin demonstrated significant reductions in mean (SEM) insulin AUC 120 minutes after OGTT (-2930 [912] vs -414 [432] microIU/mL [-20349 6334 vs -2875 3000 pmol/L]; P =.01), weight (-1.3 [0.6] vs 1.1 [0.4] kg; P =.005), and diastolic blood pressure (-5 [4] vs 5 [2] mm Hg; P =.009) vs controls, respectively [11].
• Mean (SE) changes in the AUC for serum estradiol concentrations were 4% (6%), 42% (12%), and 128% (24%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively [10].
• The area under the plasma concentration time curve (AUC) of oral digoxin was significantly lower during rifampin treatment; the effect was less pronounced after intravenous administration of digoxin [12].
• Rifampin treatment increased intestinal P-gp content 3.5 +/- 2.1-fold, which correlated with the AUC after oral digoxin but not after intravenous digoxin [12].

Chemical compound and disease context of Area Under Curve

• The day 29 etoposide or catechol area under the curve (AUC) was correlated with neutropenia (P =.027 and P =.0008, respectively) [13].
• Sex, age, 5-FU AUC, and diabetes mellitus may have an impact on the pharmacodynamics of this regimen [14].
• Although doxorubicin is one of the most commonly used antineoplastics, no studies to date have clearly related the area under the concentration-time curve (AUC) to toxicity or response [15].
• In patients with normal albumin and creatinine, increased toxicity in those older than 65 years was associated with a reduced drug clearance, and in those with increased liver enzymes by a trend toward an increase in free etoposide AUC [16].
• PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB-IV non-small-cell lung cancer received carboplatin at area under the concentration-time curve (AUC) 5 mg/mL/min and gemcitabine at an initial dose of 800 mg/m2, subsequently escalated by 100 mg/m2 per step [17].

Biological context of Area Under Curve

• Individualized carboplatin doses were calculated to achieve a target area under the concentration x time curve (AUC) and adjusted for the glomerular filtration rate (estimated by 99mTc-labeled diethylene-triamine pentaacetic acid clearance) [1].
• Phase I studies were initiated at 0.8 mg/m2 (one-tenth the equivalent LD10 in male CD1 mice), with the intent of escalating the dose by an extended factor-of-two method until the target AUC and/or maximum tolerated dose (MTD) was reached [18].
• In prevention study C (n=58), oseltamivir did not reduce infection rates (85 versus 84%) but significantly reduced median AUC virus titre (10.0 versus 66.9 log10 TCID50 x h/ml; P=0.03) and duration of viral shedding (36 versus 84 h; P=0.03) compared with placebo [19].
• RESULTS: Comparison of ara-CTP pharmacokinetics in circulating AML cells demonstrated that the area under the curve (AUC) of ara-CTP increased significantly (median, 1.8-fold; range, 1.6 to 2.4; P = .004) after fludarabine infusion [20].
• The dose versus AUC relationship was well described using a Michaelis-Menten model of brequinar elimination kinetics with Vmax = 45 (micrograms/ml)/h and Km = 123 micrograms [21].

Anatomical context of Area Under Curve

• Erythrocyte thioguanine nucleotide levels were also highly variable (range, 0 to 10 pmol/g Hgb) and did not correlate with mercaptopurine dose or AUC [22].
• The AUC and total body clearance of thioTEPA, but not of TEPA, were closely correlated with neutrophil but not platelet toxicity [23].
• CONCLUSION: We have shown that carboplatin can be delivered at an AUC of 12 for four courses without granulocyte colony-stimulating factor support, although significant hematologic toxicity occurs [24].
• Since the assay AUC of 5-FU at 50% inhibition was in a clinically achievable range for only two of the 11 cell lines, we performed a multivariate analysis to explore parameters which predict 5-FU sensitivity [25].
• Mean peak plasma 5-FU concentrations ranged from 6.19 mumol/L to greater than 60 mumol/L, and peritoneal fluid to plasma 5-FU area under the curve (AUC) ratios ranged from 85 to 1,150 [26].

Associations of Area Under Curve with chemical compounds

• Cohorts of at least three patients received carboplatin at an initial target AUC of 6 mg.min/mL, with escalations of 2 mg.min/mL in subsequent cohorts [1].
• Degree of myelosuppression was not correlated with cyclophosphamide AUC or clearance [27].
• Following continuous oral treatment, the mean day 28 AUC for all-trans RA was significantly lower than that on day 1 (213 ng/mL per hour versus 467 ng/mL per hour; P < .01), a decline significantly attenuated by ketoconazole, which increased the mean plasma all-trans RA AUC on day 29 to 375 ng/mL per hour (P < .01) [28].
• However, the effect on AUC for the major oncolytic metabolites 4-hydroxycyclophosphamide and phosphoramide mustard was not statistically significant [29].
• Twelve (60%) of the 20 had values for area under the curve (AUC) for BCNU concentration x time that exceeded 600 (micrograms/mL) x minute, whereas only two (11%) of the 18 without pulmonary injury had values above this level (P < .03) [30].

Gene context of Area Under Curve

• The interaction of PDK2 with the lipoyl domains of E2 (L1, L2) and the E3-binding protein (L3) were characterized by AUC [31].
• Except for ND4L which starts with AUC and ATPase 8 which starts with GUG, AUG is used as the initiation codon [32].
• We also show that derepression of infC, thrS, and rpsO is obtained with other 'abnormal' initiation codons such as AUA, AUC, and CUG which initiate with the same low efficiency as AUU, and also with ACG which initiates with an even lower efficiency [33].
• A larger GH increase (P < 0.02) was seen after GHRH-Arg compared to GHRH alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 1.2 +/- 0.3) [34].
• The latter group presented a higher ACTH response than controls during stimulation with hCRH alone [area under the curve (AUC) 1138 +/- 99 vs. 709 +/- 62 pmol.L/min] and hCRH/5% NaCl (AUC 1602 +/- 209 vs. 1158 +/- 187 pmol.L.min) [35].

Analytical, diagnostic and therapeutic context of Area Under Curve

• It was of note that even the oral administration of the same busulfan preparation resulted in AUC values in the same range as observed after parenteral application [36].
• Patients who achieved a complete response, partial response, or stable disease received two 21-day cycles of consolidation chemotherapy consisting of paclitaxel 200 mg/m2 IV for 3 hours and carboplatin at a dose based on an AUC of 6 mg/mL x min [37].
• Doses ranged from pemetrexed 400 mg/m(2) (as a 10-minute intravenous infusion), followed by carboplatin area under the plasma concentration-time curve (AUC) 4 mg/mL.min (as a 30-minute intravenous infusion) to pemetrexed 500 mg/m(2), carboplatin AUC 6 mg/mL.min [38].
• The formula is therefore applicable to combination and high-dose studies as well as conventional single-agent therapy, although the target AUC for carboplatin will need to be redefined for combination chemotherapy [39].
• Future clinical trials of suramin should be designed in such a way as to limit the total cumulative dose to < or = 157 mg/kg given over a period of > or = 8 weeks, limit the period of exposure to plasma suramin concentrations greater than 200 micrograms/mL to < or = 25 days, and limit the AUC greater than 200 micrograms/mL to < or = 48,000 mg.h/AL [40].

References