Pharmacokinetics of amoxicillin in obese and nonobese subjects.

AIMS: To compare the pharmacokinetics of amoxicillin (AMX) in obese and nonobese subjects, given as single dose 875-mg tablets. METHODS: A prospective, single-centre, open-label, clinical study was carried out involving 10 nonobese and 20 obese subjects given a dose of an AMX 875-mg tablet. Serial blood samples were collected between 0 and 8 hours after administration of AMX and plasma levels were quantified by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters (PK) were calculated by noncompartmental analysis and means of the 2 groups were compared using Student t-test. Analysis of correlation between covariates and PK was performed using Pearson's correlation coefficient. RESULTS: Ten nonobese subjects (mean age 30.6 ± 7.12 y; body mass index 21.56 ± 1.95 kg/m2 ) and 20 obese subjects (mean age 34.47 ± 7.03 y; body mass index 33.17 ± 2.38 kg/m2 ) participated in the study. Both maximum concentration (Cmax ; 12.12 ± 4.06 vs. 9.66 ± 2.93 mg/L) and area under the curve (AUC)0-inf (34.18 ± 12.94 mg.h/L vs. 26.88 ± 9.24 mg.h/L) were slightly higher in nonobese than in obese subjects, respectively, but differences were not significant. The volume of distribution (V/F) parameter was statistically significantly higher in obese compared to nonobese patients (44.20 ± 17.85 L vs. 27.57 ± 12.96 L). Statistically significant correlations were observed for several weight metrics vs. AUC, Cmax , V/F and clearance, and for creatinine clearance vs. AUC, Cmax and clearance. CONCLUSION: In obese subjects, the main altered PK was V/F as a consequence of greater body weight. This may result in antibiotic treatment failure if standard therapeutic regimens are administered.

Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?

This narrative review highlights the degree to which new antiobesity medications based on gut-derived nutrient-stimulated hormones (incretins) cause loss of lean mass, and the importance of resistance exercise to preserve muscle. Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight loss in randomized trials, effects that may be enhanced in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. Liraglutide and semaglutide (GLP-1RA), tirzepatide (GLP-1 and GIP receptor dual agonist), and retatrutide (GLP-1, GIP, and glucagon receptor triple agonist) are peptides with incretin agonist activity that induce ∼15-24% weight loss in adults with overweight and obesity, alongside beneficial impacts on blood pressure, cholesterol, blood glucose, and insulin. However, these agents also cause rapid and significant loss of lean mass (∼10% or ∼6 kg), comparable to a decade or more of aging. Maintaining muscle mass and function as humans age is crucial to avoiding sarcopenia and frailty, which are strongly linked to morbidity and mortality. Studies indicate that supervised resistance exercise training interventions with a duration >10 weeks can elicit large increases in lean mass (∼3 kg) and strength (∼25%) in men and women. After a low-calorie diet, combining aerobic exercise with liraglutide improved weight loss maintenance compared with either alone. Retaining lean mass during incretin therapy could blunt body weight (and fat) regain on cessation of weight loss pharmacotherapy. We propose that tailored resistance exercise training be recommended as an adjunct to incretin therapy to optimize changes in body composition by preserving lean mass while achieving fat loss.

Effects of High-Intensity Interval Training on Central Blood Pressure: A Systematic Review and Meta-Analysis. / Efeitos do Treinamento Intervalado de Alta Intensidade sobre a Pressão Arterial Central: Uma Revisão Sistemática e Metanálise.

Central blood pressure (cBP) is considered an independent predictor of organ damage, cardiovascular events and all-cause mortality. Evidence has shown that high intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness and vascular function. However, the effects of these aerobic training modalities on cBP have not yet been properly reviewed.This meta-analysis aims to investigate to effects of HIIT versus MICT on cBP.We conducted a meta-analysis of randomized controlled trials that compared HIIT versus MICT on cBP. Primary outcomes were measures of central systolic blood pressure (cSBP) and central diastolic blood pressure (cDBP). Peripheral systolic blood pressure (pSBP) and diastolic blood pressure (pDBP), pulse wave velocity (PWV) and maximal oxygen uptake (VO2max) were analyzed as second outcomes. Meta-analysis of mean differences (MD) was conducted using the random effects model.Our study included 163 patients enrolled in six trials. We found that HIIT was superior to MICT in reducing the cSBP (MD = -3.12 mmHg, 95% CI: -4.75 to -1.50, p = 0.0002) and SBP (MD = -2.67 mmHg, 95% CI: -5.18 to -0.16, p = 0.04), and increasing VO2max(MD = 2.49 mL/kg/min, 95% CI: 1.25 to 3.73, p = 0.001). However, no significant differences were reported for cDBP, DBP and PWV.HIIT was superior to MICT in reducing the cSBP, which suggests its potential role as a non-pharmacological therapy for high blood pressure.

A pressão arterial central (PAc) é considerada um preditor independente de lesão de órgão, eventos cardiovasculares e mortalidade por todas as causas. Evidências mostram que o treino intervalado de alta intensidade (HIIT) é superior ao treino contínuo de intensidade moderada (MICT) na melhoria da aptidão cardiorrespiratória e da função vascular. No entanto, os efeitos dessas modalidades de treino aeróbico sobre a PAc não foram propriamente revisados. Esta metanálise tem como objetivo investigar os efeitos do HIIT versus MICT sobre a PAc.Conduzimos uma metanálise de ensaios controlados randomizados que compararam HIIT versus MICT sobre a PAc. Os desfechos primários foram Pressão Arterial Sistólica (PAS) central (PASc) e Pressão Arterial Diastólica central (PADc). A PAS periférica (PASp), a PAD periférica (PADp), a Velocidade de Onda de Pulso (VOP) e a captação máxima de oxigênio (VO2max) foram analisadas como desfechos secundários. A metanálise das diferenças médias (DM) foi conduzida usando modelos de efeitos aleatórios.Nosso estudo incluiu 163 pacientes recrutados em seis ensaios. Encontramos que HIIT foi superior ao MICT em reduzir PASc (DM = -3,12 mmHg, IC95% -4,75 ­ 1,50, p = 0,0002) e PAS (DM = -2,67 mmHg, IC95% -5,18 ­ -0,16, p = 0,04) e aumentar VO2max (DM = 2,49 mL/Kg/min, IC95% 1,25 ­ 3,73, p = 0,001). No entanto, não foram relatadas diferenças quanto à PADc, PAD ou VOP. O HIIT foi superior ao MICT em reduzir PASc, sugerindo seu potencial papel como uma terapia não farmacológica para a pressão arterial elevada.

Cardiac autonomic control following resistance exercise with different set configurations in apparently healthy young men: A crossover study.

We compared the heart rate variability (HRV) after a low-intensity resistance exercise (LI-RE) with short (SSC/LI-RE) and long (LSC/LI-RE) set configurations, composed of 10 and 20 repetitions, respectively. Randomly, ten young males performed one session of both RE protocols. Time- and frequency-domain, and nonlinear HRV parameters were assessed at baseline and 20-30 and 50-60 min after protocols. Significant reductions in time-domain, frequency-domain and nonlinear HRV parameters were observed at 20-30 min and 50-60 min after LSC/LI-RE compared to baseline. A low-intensity RE with a long set configuration induces an acute vagal withdrawal and loss of heart rate complexity after exercise.

Tri-ponderal mass index as a tool for insulin resistance prediction in overweight adolescents: A cross-sectional study.

OBJECTIVE: The aims of this study were to assess the capacity of tri-ponderal mass index (TMI) to screen and predict insulin resistance (IR) in overweight Brazilian adolescents, comparing it with body mass index (BMI) predictive capacity; and to verify the IR predictive capacity of other assessment tools such as waist circumference (WC), and waist-to-height ratio (WHR). METHODS: A cross-sectional study was carried out with 217 overweight adolescents, from both sexes, between 12 and 18 y of age. The participants were classified as having IR according to a previous established cutoff point of ≤3.16. IR was determined by the homeostasis model assessment of insulin resistance. The other assessment tools were measured with standard protocols. RESULTS: There was no difference between TMI and BMI to explain the presence of IR. In girls, BMI presented a slightly better predictive capacity to explain IR than TMI. Moreover, WC was reported to be the most effective IR screening methods for girls. Receiver operating characteristic curves showed that TMI and BMI presented similar values of sensibility and specificity for boys. Nevertheless, BMI had a better sensibility and TMI had a better specificity for girls. Interestingly, WC demonstrated a strong sensibility for both sexes. CONCLUSIONS: TMI did not present a superior predictive accuracy for IR screening in overweight Brazilian adolescents when compared with BMI. TMI and BMI presented similar values of sensitivity and specificity for boys and WC a slightly superior IR predictive capacity for girls.

Efeitos do Treinamento Intervalado de Alta Intensidade sobre a Pressão Arterial Central: Uma Revisão Sistemática e Metanálise / Effects of High-Intensity Interval Training on Central Blood Pressure: A Systematic Review and Meta-Analysis

Resumo A pressão arterial central (PAc) é considerada um preditor independente de lesão de órgão, eventos cardiovasculares e mortalidade por todas as causas. Evidências mostram que o treino intervalado de alta intensidade (HIIT) é superior ao treino contínuo de intensidade moderada (MICT) na melhoria da aptidão cardiorrespiratória e da função vascular. No entanto, os efeitos dessas modalidades de treino aeróbico sobre a PAc não foram propriamente revisados. Esta metanálise tem como objetivo investigar os efeitos do HIIT versus MICT sobre a PAc.Conduzimos uma metanálise de ensaios controlados randomizados que compararam HIIT versus MICT sobre a PAc. Os desfechos primários foram Pressão Arterial Sistólica (PAS) central (PASc) e Pressão Arterial Diastólica central (PADc). A PAS periférica (PASp), a PAD periférica (PADp), a Velocidade de Onda de Pulso (VOP) e a captação máxima de oxigênio (VO2max) foram analisadas como desfechos secundários. A metanálise das diferenças médias (DM) foi conduzida usando modelos de efeitos aleatórios.Nosso estudo incluiu 163 pacientes recrutados em seis ensaios. Encontramos que HIIT foi superior ao MICT em reduzir PASc (DM = -3,12 mmHg, IC95% -4,75 - 1,50, p = 0,0002) e PAS (DM = -2,67 mmHg, IC95% -5,18 - -0,16, p = 0,04) e aumentar VO2max (DM = 2,49 mL/Kg/min, IC95% 1,25 - 3,73, p = 0,001). No entanto, não foram relatadas diferenças quanto à PADc, PAD ou VOP. O HIIT foi superior ao MICT em reduzir PASc, sugerindo seu potencial papel como uma terapia não farmacológica para a pressão arterial elevada.

Abstract Central blood pressure (cBP) is considered an independent predictor of organ damage, cardiovascular events and all-cause mortality. Evidence has shown that high intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness and vascular function. However, the effects of these aerobic training modalities on cBP have not yet been properly reviewed.This meta-analysis aims to investigate to effects of HIIT versus MICT on cBP.We conducted a meta-analysis of randomized controlled trials that compared HIIT versus MICT on cBP. Primary outcomes were measures of central systolic blood pressure (cSBP) and central diastolic blood pressure (cDBP). Peripheral systolic blood pressure (pSBP) and diastolic blood pressure (pDBP), pulse wave velocity (PWV) and maximal oxygen uptake (VO2max) were analyzed as second outcomes. Meta-analysis of mean differences (MD) was conducted using the random effects model.Our study included 163 patients enrolled in six trials. We found that HIIT was superior to MICT in reducing the cSBP (MD = -3.12 mmHg, 95% CI: -4.75 to -1.50, p = 0.0002) and SBP (MD = -2.67 mmHg, 95% CI: -5.18 to -0.16, p = 0.04), and increasing VO2max(MD = 2.49 mL/kg/min, 95% CI: 1.25 to 3.73, p = 0.001). However, no significant differences were reported for cDBP, DBP and PWV.HIIT was superior to MICT in reducing the cSBP, which suggests its potential role as a non-pharmacological therapy for high blood pressure.