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Felcisetrag (formerly known as TAK-954) is a selective serotonin receptor agonist under investigation for use in patients with postoperative gastrointestinal dysfunction. The safety, tolerability, and pharmacokinetics (PK) of intravenous (i.v.) felcisetrag have been studied, but little is known about the effect of hepatic impairment on the PK of the drug. This phase 1, non-randomized, open-label study compared the PK of a single 60-minute i.v. infusion of felcisetrag between healthy individuals (n = 8) and patients with moderate (n = 10) or severe (n = 7) hepatic impairment. The primary study end points were the total and free maximum observed plasma concentration of felcisetrag at the end of infusion (C max ), area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC last ), and AUC from time 0 to infinity (AUC inf ). Concentration-time profiles of felcisetrag were similarly shaped between groups but revealed lower concentrations of total plasma felcisetrag with increasing severity of hepatic impairment, whereas concentrations of free felcisetrag increased. The ratios of AUC last and AUC inf for patients with severe hepatic impairment were up to 29.3% lower for total felcisetrag and up to 29.2% higher for free felcisetrag than found in healthy individuals (P < .05). Infusions were well tolerated with no discontinuations, severe adverse events, or deaths during the study. Overall, the effect of hepatic impairment on exposure to felcisetrag was minimal, suggesting that dose adjustment may be unnecessary in patients with hepatic impairment., (© 2022 Takeda Pharmaceutical Company Limited. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

The 5-hydroxytryptamine type-4 receptor agonist felcisetrag (TAK-954) is being investigated for improving gastrointestinal motility in postoperative gastrointestinal dysfunction. Polypharmacy often occurs in this setting, and as in vitro data indicate, felcisetrag is primarily metabolized by cytochrome P450 (CYP) 3A4, its CYP3A4-mediated drug-drug interaction potential requires consideration. This phase 1, fixed-sequence, open-label, crossover trial (ClinicalTrials.gov identifier NCT03173170) investigated the effect of itraconazole, a potent CYP3A4 inhibitor, on felcisetrag pharmacokinetics in healthy adults. Over 2 study periods (period 1, 6 days; period 2, 9 days), participants received a single felcisetrag 0.2-mg intravenous dose (day 1, period 1; and day 4, period 2), and once-daily oral itraconazole 200-mg doses (days 1-8, period 2). For felcisetrag alone, felcisetrag total systemic exposure was lower than with itraconazole coadministration. The geometric mean ratio for area under the plasma concentration-time curve from time 0 to infinity of felcisetrag plus itraconazole: felcisetrag alone was 1.49 (90% confidence interval, 1.39-1.60). Peak exposure was similar between regimens (geometric mean ratio, 1.06; 90% confidence interval, 0.96-1.18), and both treatments were well tolerated. These data suggest limited CYP3A4-mediated drug-drug interaction inhibition for felcisetrag., (© 2022, The American College of Clinical Pharmacology.)

The purpose of this study was to determine if high school females differed in individual measures of health-related physical fitness, barriers to exercise, or activity level based on ethnicity or socioeconomic status. A cross-sectional sample consisting of African American (28%), Hispanic (23%), and white (49%) female high school students, 46% from low socioeconomic groups and 54% from moderate or high socioeconomic groups (n = 1314, age = 16.2 +/- 0.9) participated in this study. A 15-question survey instrument assessed barriers to exercise and activity level. The FITNESSGRAM fitness test assessed aerobic capacity and body mass index (BMI), and skinfold calipers were used to assess percent body fat. Significant differences between African Americans, Hispanics, and whites were found on the following dependent variables: BMI, percent fat, mile run, perceived barriers to exercise, and activity level. Significant differences between socioeconomic groups were found on the following dependent variables: percent fat, mile run, activity level, and perceived barriers to exercise. These results suggest that students of minority and low socioeconomic groups should be given separate and different interventions regarding health-related fitness.

Background: Immunoglobulin A deficiency is more common in patients with coeliac disease and also in patients with other gastrointestinal diseases than in normal people. There is a concern, therefore, that routine serum immunoglobulin (Ig) A testing of all cases of suspected coeliac disease may lead to unnecessary biopsy., Methods: Four hundred eighty-two routine consecutive samples from cases of suspected coeliac disease or malabsorption (109 children) were tested for IgA anti-endomysium and total IgA. Four hundred twenty-four sera samples also had IgG antigliadin checked for high-titre antibody. Archived adult sera from 31 patients with coeliac disease and 52 disease control subjects were included in the study., Results: Seven routine cases with serum IgA less than 15% of the mean normal for age and four cases with undetectable IgA were identified. Four patients, including three of four with clear deficiency, underwent small bowel biopsy, and all four had normal histologic findings and normal intraepithelial lymphocyte counts. Only one of the seven had high-titre IgG antigliadin antibody but that patient had normal histologic findings. One (3%) of 31 adults with established coeliac disease and 1 (2%) of 52 control subjects were IgA deficient., Conclusions: Of patients with IgA deficiency, only those with both IgA deficiency and high-titre IgG antigliadin antibody should be routinely considered for biopsy.

The modified Harvard Step Test and a 70-item questionnaire based on the Health Belief Model (HBM) were given to 257 high school students, 154 blacks, and 93 whites. Mean age of students was 16.0 years (SD = 1.1) for whites and 15.8 years (SD = 1.1) for blacks. Though more blacks than whites were in poor physical condition (51% females and 27% males vs. 35% females and 16% males, respectively), the difference was not statistically significant. A high level of concurrence existed between individuals in good physical condition and those who stated they regularly exercised, but this agreement was more pronounced among white students (73% vs. 62% for black students). White students were significantly more knowledgeable than black students on the exercise knowledge subscale. No significant differences existed between black and white students on any other HBM subscales. When subscale scores for those in good versus poor physical condition were compared, significant differences were found on all subscales except the perceived benefits subscale. Analysis of individual questionnaire items which best predicted whether one was in poor or good physical condition found four items accounted for 38% of variance in black students, and seven items accounted for 52% of variance in white students.