Pulmonary Pharmacokinetic and Pharmacodynamic Evaluation of Ampicillin/Sulbactam Regimens for Pneumonia Caused by Various Bacteria, including Acinetobacter baumannii.

This study aimed to assess the dosing regimens of ampicillin/sulbactam for pneumonia based on pulmonary pharmacokinetic (PK)/pharmacodynamic (PD) target attainment. Using the literature data, we developed pulmonary PK models and estimated the probabilities of attaining PK/PD targets in lung tissue. Against bacteria other than A. baumannii (the general treatment), the PK/PD target was set as both 50% time above the minimum inhibitory concentration (T > MIC) for ampicillin and 50% T > 0.5 MIC for sulbactam. For the A. baumannii treatment, the PK/PD target was set as 60% T > MIC for sulbactam. The pulmonary PK/PD breakpoint was defined as the highest minimum inhibitory concentration (MIC) at which the target attainment probability in the lung tissue was ≥90%. The lung tissue/serum area under the drug concentration-time curve from 0 to 3 h (AUC0-3h) ratios for ampicillin and sulbactam were 0.881 and 0.368, respectively. The ampicillin/sulbactam AUC0-3h ratio in the lung tissue was 3.89. For the general treatment, the pulmonary PK/PD breakpoint for ampicillin/sulbactam at 3 g four times daily in typical patients with creatinine clearance (CLcr) of 60 mL/min was 2 µg/mL, which covered the MIC90s (the MICs that inhibited the growth of 90% of the strains) of most gram-positive and gram-negative bacteria. For the A. baumannii treatment, the pulmonary PK/PD breakpoint for ampicillin/sulbactam at 9 g 4-h infusion three times daily (27 g/day) in patients with a CLcr of 60 mL/min was 4 µg/mL, which covered the MIC90 of A. baumannii. A PK/PD evaluation for pneumonia should be performed in the lung tissue (the target site) rather than in the blood because sulbactam concentrations are lower in lung tissue. These findings should facilitate the selection of ampicillin/sulbactam regimens for pneumonia caused by various bacteria, including A. baumannii.

Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid-associated thrombocytopenia.

WHAT IS KNOWN AND OBJECTIVE: Linezolid (LZD) may cause thrombocytopenia, which can result in discontinuation of treatment. In this study, the blood LZD trough concentration was estimated based on population pharmacokinetic (PK) parameters derived from two previously published models in the Japanese population to determine the rate of achieving the target trough value when the risk of thrombocytopenia is low and to clarify its relationship with the onset of thrombocytopenia. METHODS: This study included adult patients hospitalized at Shimane University Hospital, who received LZD treatment for at least 4 days from January 2010 to December 2017. Patients whose platelet count fell below 70% before LZD administration were categorized as the thrombocytopenic group. Patient PK parameters were calculated based on the population PK models described by Matsumoto et al. and Sasaki et al., and these parameters were designated A and B, respectively. Based on these parameters, the rate of achieving an LZD trough concentration of less than 8 µg/ml, which is the safety target achievement rate, was calculated using a random simulation for each patient. We further analysed the association between the incidence of thrombocytopenia and patient factors, including safety target achievement rate, through univariate, multivariate, and receiver operating characteristic (ROC) analyses. RESULTS AND DISCUSSION: Patients (n = 77) aged 72 ± 11 years and weighing 56.7 ± 10.9 kg, with a creatinine clearance (CLcr ) of 60.5 ± 47.2 ml/min and a cirrhosis prevalence of 9.1%, were analysed. All patients received LZD at a dose of 600 mg twice daily for a total of 10.9 ± 8.9 days. Univariate analyses revealed significant differences (p < 0.05) in the duration of LZD therapy, serum creatinine, creatinine clearance, LZD clearance, and the safety target achievement rate for parameters A and B between the thrombocytopenic and non-thrombocytopenic groups. A multivariate analysis of these factors stratified with the cutoff values obtained by ROC analysis revealed that the duration of LZD therapy and the safety target achievement rates for parameters A and B were significant factors (odds ratios for duration of LZD therapy: 7.436 [95% confidence interval (CI): 1.918-28.831] and 4.712 [95% CI: 1.567-14.163]; odds ratio for safety target achievement rate: 0.060 [95% CI: 0.016-0.232] and 0.167 [95% CI: 0.056-0.498] for parameters A and B, respectively). When the safety target achievement rates for patients treated with LZD were compared between the thrombocytopenic and non-thrombocytopenic groups, the safety target achievement rate was higher in the non-thrombocytopenic group in both the patients treated with LZD for less than 10 days and those for 10 days or more. Therefore, the safety target achievement rate estimated by the PK/PD simulation may represent to be an important index for risk assessment of LZD-induced thrombocytopenia. WHAT IS NEW AND CONCLUSION: The risk of LZD-induced thrombocytopenia, which increased with the duration of LZD therapy, may be predicted using the safety target achievement rate obtained by the blood concentration simulation.

Pharmacodynamic Evaluation of Ampicillin-sulbactam in Pediatric Patients Using Plasma and Urine Data.

BACKGROUND: We aimed to develop population pharmacokinetic (PK) models of ampicillin and sulbactam using pooled data analysis and to optimize dosing regimens of ampicillin-sulbactam (combination ratio of 2:1) in pediatric patients. METHODS: Population PK models of ampicillin and sulbactam were separately developed by simultaneously fitting plasma and urine data from pediatric patients in 14 published studies. Based on these models, we estimated the probability of attaining a pharmacodynamic (PD) target [50% of time that free drug concentrations above the minimum inhibitory concentration, 50% fT > minimum inhibitory concentration (MIC)] against MIC90 [MIC that blocked the growth of 90% of the strains] of common bacteria in community-acquired pneumonia. RESULTS: The analysis included 54 pediatric patients (0.083-16.42 years of age, 4.0-77.0 kg of body weight). A total of 284 plasma concentrations and 90 urinary excretions from 0 to 6 hours after administration were used for population PK modeling. The data were adequately described by 2-compartment models for ampicillin and sulbactam. Age was not a statistically significant covariate in the PK of either drug. The PK/PD breakpoint MICs for 45 mg/kg 3 times daily and 75 mg/kg 4 times daily (q.i.d.) were 0.25 and 1 µg/mL, respectively. For empiric therapy of community-acquired pneumonia, because MIC90 values for the main target pathogens is high (MIC90 = 2 µg/mL for Streptococcus pneumoniae and MIC90 = 4 µg/mL for Haemophilus influenzae), 75 mg/kg q.i.d. (Food and Drug Administration-approved maximum dosage in United States) might be better than 45 mg/kg 3 times daily (within approved dosage in Japan) to cover many pathogens. CONCLUSIONS: From the results of this PK/PD approach, 75 mg/kg q.i.d. (Food and Drug Administration-approved maximum dosage) should be recommended in the empiric therapy of community-acquired pneumonia.

[Clinical Pharmacometrics Research Aimed at Individual Optimization of Infectious Disease Treatment against Antimicrobial Resistant Bacteria].

In recent years, antimicrobial resistance bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) have become a global problem. One of the countermeasures is to optimize the use of antimicrobial drugs, specifically to optimize the dosage and administration based on the therapeutic drug monitoring (TDM) and pharmacokinetics (PK)/pharmacodynamics (PD) theory. On the other hand, in clinical practice, clinical-pharmacometrics can be used for optimized management of individual patients of pharmaceutical products. Therefore, we aimed at individual optimization of infectious disease treatment for antimicrobial resistant bacteria, and tried a series of flows from model construction to clinical application, that is, practice of clinical pharmacometrics. In the context of individual optimization and optimization management of drug therapy in the medical field, it is considered that hospital pharmacists can contribute to the improvement of infectious disease treatment of antimicrobial resistance bacteria by contributing to the optimization of administration method. In addition, clinical pharmacometrics can be applied not only to antibacterial drugs but also to all drugs, and can be said to be a useful method for quantitatively evaluating the promotion of individualized administration methods for patients.

[Assessment of Renal Function and Simulation Using Serum Cystatin-C in an Elderly Patient with Uncontrollable Plasma Vancomycin Levels Due to Muscular Dystrophy: A Case Report].

Herein, we describe a case of an elderly patient with muscular dystrophy for whom control of the plasma vancomycin (VCM) concentration proved difficult when he developed a catheter-related bloodstream infection. The pharmacist initially carried out therapeutic drug monitoring using an estimate of the creatinine clearance (CLcr) level, which was based on the serum creatinine (SCr) and serum cystatin-C (CysC) levels, but was ultimately unable to control the plasma VCM concentration. Therefore, the plasma VCM concentration was predicted ex post facto using population pharmacokinetic parameters as a covariate; that is, directly including the glomerular filtration rate (GFRCysC) estimated from the CysC level, which is not affected by the muscle mass. As a result, the estimated VCM concentration was closer to the actual concentration than that predicted using CLcr. Furthermore, the results of examining the predictive accuracy according to the assessment of renal function at the time of initial VCM administration suggested that estimation of the trough concentration using GFRCysC might be useful in elderly patients with muscular dystrophy.

Pharmacokinetics of edoxaban in EGFR-mutated non-small cell lung cancer patients with venous thromboembolism.

BACKGROUND: The risk of venous thromboembolism (VTE) is increased 7-fold in patients with cancer than in those without. Low-molecular-weight heparin is the standard treatment for cancer-associated VTE. Direct oral anticoagulants (DOACs) are not inferior to low-molecular-weight heparin with respect to the general outcome of recurrent VTE. Warfarin is associated with a risk of bleeding when used in combination with gefitinib or erlotinib which are epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). It is unclear, however, whether combination treatments with EGFR-TKIs and DOACs pose the same risk. We aimed to identify anticancer drugs and anticoagulants that can be used safely in combination, as accompanying research to an observational study on VTE incidence rates in lung cancer patients (Rising-VTE/NEJ037 study). METHODS: Twelve patients receiving EFGR-TKI monotherapy and VTE treatment were enrolled. Blood samples were collected in time series after the first dose of edoxaban, and further samples were collected within 8-15 days after administering EGFR-TKIs. The pharmacokinetics (PK) of edoxaban were analyzed using a non-compartmental model. RESULTS: Edoxaban concentrations (30 mg once daily) were measured in eight patients. PK analyses showed no significant differences before and after co-administration of EGFR-TKIs (gefitinib, erlotinib, and afatinib). CONCLUSIONS: Our findings indicate that the PK of edoxaban was not considerably affected by co-administration of EGFR-TKIs (gefitinib, erlotinib, and afatinib).

Prostatic Pharmacokinetic/Pharmacodynamic Evaluation of Ampicillin-Sulbactam for Bacterial Prostatitis and Preoperative Prophylaxis.

This study aims to define the penetration of ampicillin and sulbactam into prostate tissue, develop a prostatic pharmacokinetic model of each drug, and assess the appropriateness of ampicillin-sulbactam regimens for the treatment of prostatitis and the prophylaxis of postoperative infection, based on a pharmacokinetic and pharmacodynamic simulation. Subjects were prostatic hyperplasia patients prophylactically receiving a 0.5-hour infusion of 1.5 g (1:0.5 g) or 3 g (2:1 g) ampicillin-sulbactam before transurethral resection of the prostate. Ampicillin and sulbactam concentrations in plasma and prostate tissue were measured. The prostate tissue/plasma ratios of both ampicillin and sulbactam were approximately 0.37 (area under the drug concentration-time curve), and penetration was similar. The prostatic population pharmacokinetic model, which included a covariate analysis, adequately predicted prostate tissue concentrations in our patient population. For therapeutic use, aiming for a bactericidal target of 50% of time above minimum inhibitory concentration (T > MIC) in prostate tissue, 3 g ampicillin-sulbactam 4 times daily achieved ≥90% expected probability against only Enterococcus faecalis in typical patients with a creatinine clearance (CLcr ) of 30 mL/min. For prophylactic use, aiming for a bacteriostatic target of 30% T > MIC, 3 g ampicillin-sulbactam 4 times daily achieved ≥90% expected probability of attaining the bacteriostatic target against E. faecalis and Proteus species when CLcr was 30 mL/min. Based on prostatic simulations, the present study provides helpful recommendations for the treatment of bacterial prostatitis and preoperative prophylaxis in prostatectomy.

Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Simulation of Piperacillin/Tazobactam for Dosing Optimization in Late Elderly Patients with Pneumonia.

The aim of this study was to develop a population pharmacokinetic model for piperacillin (PIPC)/tazobactam (TAZ) in late elderly patients with pneumonia and to optimize the administration planning by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. PIPC/TAZ (total dose of 2.25 or 4.5 g) was infused intravenously three times daily to Japanese patients over 75 years old. The plasma concentrations of PIPC and TAZ were determined using high-performance liquid chromatography and modeled using the NONMEM program. PK/PD analysis with a random simulation was conducted using the final population PK model to estimate the probability of target attainment (PTA) profiles for various PIPC/TAZ-regimen-minimum-inhibitory-concentration (MIC) combinations. The PTAs for PIPC and TAZ were determined as the fraction that achieved at least 50% free time > MIC and area under the free-plasma-concentration-time curve over 24 h ≥ 96 µg h/mL, respectively. A total of 18 cases, the mean age of which was 86.5 ± 6.0 (75-101) years, were investigated. The plasma-concentration-time profiles of PIPC and TAZ were characterized by a two-compartment model. The parameter estimates for the final model, namely the total clearance, central distribution volume, peripheral distribution volume, and intercompartmental clearance, were 4.58 + 0.061 × (CLcr - 37.4) L/h, 5.39 L, 6.96 L, and 20.7 L/h for PIPC, and 5.00 + 0.059 × (CLcr - 37.4) L/h, 6.29 L, 7.73 L, and 24.0 L/h for TAZ, respectively, where CLcr is the creatinine clearance. PK/PD analysis using the final model showed that in drug-resistant strains with a MIC > 8 µg/mL, 4.5 g of PIPC/TAZ every 6 h was required, even for the patients with a CLcr of 50-60 mL/min. The population PK model developed in this study, together with MIC value, can be useful for optimizing the PIPC/TAZ dosage in the over-75-year-old patients, when they are administered PIPC/TAZ. Therefore, the findings of present study may contribute to improving the efficacy and safety of the administration of PIPC/TAZ therapy in late elderly patients with pneumonia.

Implications of Albumin Leakage for Survival in Maintenance Hemodialysis Patients: A 7-year Observational Study.

Albumin leakage during hemodialysis (HD) presents a clinical dilemma. However, protein-binding uremic toxins are suggested to be responsible for increased mortality. No one has investigated the relationship between albumin leakage and mortality. Therefore, the purpose of this observational study was to analyze the association of albumin leakage with mortality in 690 HD patients who survived one year after enrollment. They were divided to three groups who received HD with large (3 g or more per HD session), middle (1 to 3 g) or small (less than 1 g) amount of albumin leakage, respectively. A propensity score analysis minimizing indication bias was performed. Consequently, in a 7-year observation period, 212 patients died. Albumin leakage 3 g or more per HD session provided better prognosis than albumin leakage less than 3 g per HD session. In conclusion, clinically acceptable large albumin leakage provides beneficial effects on mortality in maintenance HD patients.

Identification of cysteinylated transthyretin, a predictive biomarker of treatment response to partially hydrolyzed guar gum in type 2 diabetes rats, by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

Recent evidence has indicated that total fiber intake is inversely related to type 2 diabetes risk. The present study aimed to investigate the effects of chronic administration of partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, on the occurrence of diabetes and its complications, fatty liver and nephropathy. We also identified predictive serum biomarkers of treatment response to PHGG by mass spectroscopy-based proteomic analysis using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a good model of human non-insulin-dependent diabetes mellitus. In this study, at 5 weeks of age, OLETF rats and control strain Long-Evans Tokushima Otsuka (LETO) rats were fed a control diet or a high-fiber diet (5% PHGG) for 57 weeks. Body weight, food intake, oral glucose tolerance test, plasma insulin levels, and urine glucose and protein levels were regularly measured. Oral glucose tolerance tests (OGTT) and storage of serum in a deep freezer were conducted at the beginning of the experiment and every 4 weeks after overnight fasting during the experiments. PHGG treatment affected neither meal patterns nor the body weight of OLETF and LETO rats. Repeated measure analysis of variance revealed significant differences in fasting plasma glucose and plasma glucose at 2 h after OGTT between control OLETF (OLETF-C) rats and OLETF rats treated with PHGG (OLETF-F). The glucose response determined by the area under the curve of OGTT was significantly greater in OLETF-C rats than that in OLETF-F rats at 25 weeks of age. HOMA-IR, an index of insulin resistance, increased at 25 weeks of age in OLETF-C rats, while this increase was significantly inhibited in OLETF-F rats. At 62 weeks of age, PHGG treatment significantly improved hepatic steatosis as well as renal mesangial matrix accumulation in OLETF rats. To identify the risk marker for diabetes mellitus by SELDI-TOF MS, we collected sera from 21-week-old individuals. Among the 12 specific peaks that were risk marker candidates for diabetes mellitus, the m/z 13,720 peak was identified as that of cysteinylated transthyretin by sequencing of four tryptic peptides using tandem mass spectrometry and peak distribution around the m/z 13,720 peak in the SELDI-TOF spectra. In conclusion, we found that chronic treatment with PHGG improved insulin resistance, delayed the onset of diabetes, and inhibited the development of diabetic complications, as well as identified cysteinylated transthyretin as a predictive biomarker of treatment response to PHGG in OLETF rats.

Post-meal perceivable satiety and subsequent energy intake with intake of partially hydrolysed guar gum.

Partially hydrolysed guar gum (PHGG), a soluble dietary fibre, has been shown to provide many health benefits. Previous studies had suggested that the combination of PHGG with protein provided a significant satiation effect on visual analogue scales (VAS). What was lacking was only the effect of administration of small doses of PHGG on post-meal satiation and subsequent energy intake. The objectives of the present investigations were to find the subjective perception of post-meal satiety with acute and long term administration of small amounts of PHGG alone with food, its effects on subsequent energy intake and the comparative effects among different types of soluble fibres. The following three separate studies were conducted: in study 1, healthy subjects (n 12) consumed PHGG along with breakfast, lunch and an evening snack; in study 2, healthy subjects (n 24) consumed 2 g of PHGG or dextrin along with yogurt as breakfast for 2 weeks; in study 3, healthy subjects (n 6) took 6 g each of either PHGG or indigestible dextrin or inulin along with lunch. In all the studies, various satiety parameters were measured on VAS before and after consumption of PHGG. The addition of PHGG showed significant (P < 0.05) acute (studies 1 and 3) and long-term (studies 1 and 2) satiety effects compared to the control and/or an equal amount of carbohydrate or other types of soluble fibre. Study 2 also indicated that the prolonged consumption of PHGG may significantly (P < 0.05) reduce energy intake from whole-day snacking. PHGG could be an ideal natural soluble fibre for delivering acute and long term satiety effects for comfortable appetite control.

Evaluation of a pharmacokineticpharmacodynamic approach using software to optimize the carbapenem antibiotic regimen.

OBJECTIVE: Meropenem (MEPM) and doripenem (DRPM), whose antipseudomonal activity is more potent than that of other carbapenem antimicrobials, were used in the study. Monte Carlo simulation of drug concentrations was performed to develop an administration plan for MEPM and DRPM that takes into account the pharmacokinetics (PK)-pharmacodynamics (PD) of MEPM and DRPM and the renal function of each patient. Drug administration plans were proactively applied to patients with pneumonia to determine the usefulness of the method by assessing treatment efficacy and safety. METHODS: Patients with healthcareassociated pneumonia and an indication for MEPM or DRPM chemotherapy underwent drug administration in accordance with the MEPM and DRPM treatment plan developed by the PK-PD software applications. The primary efficacy endpoints were the clinical and bacteriological efficacy of the drugs agains pneumonia. The safety of the antimicrobials was assessed based on abnormal laboratory findings and the seizure disorders in accordance with the criteria for safety evaluation of antimicrobial agents. RESULTS: This study examined 12 and 11 patients in the MEPM and DRPM group, respectively; however, 3 DRPM patients were excluded due to the administration of anti-methicillin-resistant Staphylococcus aureus drugs after the initiation of DRPM treatment. MEPM and DRPM drug administration was determined to be safe and effective in all patients. CONCLUSIONS: The present results suggest that the Monte Carlo simulation-based PK-PD software is an effective tool for planning individualized antimicrobial chemotherapy with carbapenem in accordance with the PK-PD theory of antimicrobials. It is also possible to propose safe and effective drug administration plans for patients with healthcare-associated pneumonia.

Nephrotoxicity induced by piperacillin­tazobactam in late elderly Japanese patients with nursing and healthcare associated pneumonia.

This study aimed to clarify the efficacy, safety, and pharmacokinetics of piperacillin­tazobactam (PIPC­ TAZ) in late elderly Japanese patients. This is the first antimicrobial pilot study in late elderly patients with nursing and healthcare associated pneumonia. After PIPC­TAZ administration, PIPC concentrations in plasma were measured chromatographically and the pharmacokinetic parameters were estimated. Efficacy, safety, and bacteriological evaluations were also carried out. The mean age was 85.0 years old and most of the patients were late elderly. Chest X-rays, body temperature, white blood cell count, and C reactive protein all improved significantly, and a high efficacy ratio of 90.9% was observed. Serious nephrotoxicity was observed in 4 cases (18.2%) after administration of PIPC­TAZ. Creatinine clearance (meanS.D.) measured before PIPC­TAZ therapy was significantly lower in the nephrotoxicity group (32.54.4 mL/min) than in the non-nephrotoxicity group (46.116.7 mL/min), although the ages were not different between the 2 groups. In the pharmacokinetic parameters for PIPC, total clearance was slightly lower in the nephrotoxicity group than in the non-nephrotoxicity group. However, no significant difference was observed in plasma PIPC levels between the 2 groups. In patients with renal impairment, especially with a creatinine clearance of <40 mL/ min, renal impairment was found to be an influencing factor for severe nephrotoxicity following PIPC­TAZ administration. In conclusion, the results suggest that physicians should pay close attention in order to avoid possible toxicity, and that deliberate administration planning and careful follow-up are required in late elderly patients with comprised organ dysfunction.

Partially hydrolyzed guar gum affects the expression of genes involved in host defense functions and cholesterol absorption in colonic mucosa of db/db male mice.

Biomedical evidence in the last 20 years has shown that the consumption of partially hydrolyzed guar gum may influence lipid and/or carbohydrate metabolism at many levels. Since intestine represents the first interface to interact with dietary partially hydrolyzed guar gum in vivo, we evaluated gene expression profiles in small intestinal mucosa of db/db mice fed with partially hydrolyzed guar gum in an effort to delineate its effect on the small intestine. DNA microarray and real-time PCR analyses were performed to evaluate the gene expression profiles in mice small intestinal mucosa. Among the 28,853 transcripts represented on the GeneChip® microarray, no more than 20 genes exhibited up- or down-regulation by 1.5-fold or more after four weeks following partially hydrolyzed guar gum consumption. No adverse effects were apparent. We detected up- or down-regulation of some genes known to be involved in host defense functions and cholesterol absorption.

Hydrolyzed guar gum decreases postprandial blood glucose and glucose absorption in the rat small intestine.

We hypothesized that infusing partially hydrolyzed guar gum (PHGG) into the duodenum would reduce increases in postprandial plasma glucose by decreasing the rate of glucose diffusion from the small intestine luminal digesta of the rat. The postprandial plasma glucose and apparent glucose disappearance from the small intestine were measured after infusing artificial digesta containing 0 (control), 3.0, or 6.0 g/L PHGG into the duodenum via a cannula under anesthesia in experiments 1 and 2. The diffusion of glucose in the artificial digesta was estimated using dialysis tubing, filled with the same artificial digesta, soaked in a buffer in experiment 3. In experiment 1, the plasma glucose concentration was lower in the digesta containing 3.0 and 6.0 g/L PHGG than in the control digesta at 120 minutes (P < .05). The plasma insulin concentration was lower for the digesta containing 6.0 g/L PHGG than for the control digesta at 60 minutes (P < .05) and lower for the digesta containing 6.0 g/L PHGG than for that containing 3.0 g/L PHGG at 120 minutes (P < .05).The area under the curve of plasma glucose and insulin (experiment 1), apparent disappearance of glucose in the lumen of the small intestine (experiment 2), and net disappearance of glucose in the dialysis tube depended negatively on the viscosity of the artificial digesta (P < .05, .05, .001, and .05), which was increased by adding PHGG. Therefore, PHGG can decrease the postprandial blood glucose by lowering the rate of absorption from the small intestine in the rat by reducing the diffusion of glucose in the lumen.

Antioxidant properties of casein calcium peptides and their effects on lipid oxidation in beef homogenates.

The antioxidant activity of casein calcium peptides in several in vitro assay systems was investigated. Casein calcium peptides were prepared by the microbial enzymic hydrolysis of casein calcium. The main peak of the molecular mass distribution of the peptides was about 3 kDa. Casein calcium peptides showed strong antioxidant activity with the beta-carotene bleaching method, and they also showed scavenging activity against radicals such as superoxide radicals, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and hydroxyl radicals. Antioxidant activity was increased with an increasing peptide concentration. Casein calcium peptides also showed strong antioxidant activity against lipid oxidation in ground beef homogenates. These results suggest that casein calcium peptides are a suitable natural antioxidant that prevents the lipid oxidation of meat and related food ingredients.