Nobuhiro Yasuno

Bio: Nobuhiro Yasuno is an academic researcher from Teikyo University. The author has contributed to research in topics: Medicine & Pharmacist. The author has an hindex of 5, co-authored 23 publications receiving 107 citations. Previous affiliations of Nobuhiro Yasuno include East Tennessee State University & University of Tokyo.

Proposal of a Pharmacokinetically Optimized Dosage Regimen of Antibiotics in Patients Receiving Continuous Hemodiafiltration

Abstract: The aim of the study was to quantitatively predict the clearance of three antibiotics, amikacin, vancomycin, and teicoplanin, during continuous hemodiafiltration (CHDF) and to propose their optimal dosage in patients receiving CHDF. For this goal, in vitro CHDF experiments with a polyacrylonitrile (PAN) membrane were first performed using these antibiotics, and then the clearances were compared with in vivo CHDF situations determined in 16 critically ill patients. The in vitro CHDF clearances were described as the product of the outflow rate of a drain (Q(outflow)) and the drug unbound fraction in artificial plasma, indicating that drug adsorption to the PAN membrane has minor effect on drug clearance in our settings. The observed in vivo clearances also agreed very well with the predicted values, with a product of Q(outflow) and plasma unbound fraction, when residual creatinine clearance (CL(CR)) was taken into account (within a range of 0.67- to 1.5-fold for 15 of 16 patients). Based on these results, a nomogram of the optimized dosages of amikacin, vancomycin, and teicoplanin was proposed, and it was evident that Q(outflow) and residual CL(CR) are major determinants of the dosage and dosing interval for these antibiotics. Although the applicability needs to be confirmed with another type of membrane or higher Q(outflow), our nomogram can help determine the dosage setting in critically ill patients receiving CHDF.

Development and clinical application of high performance liquid chromatography for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine.

Abstract: A high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine or caffeine metabolites. The method is simple and of practical use because it is applicable even to plasma samples from patients who take caffeine-containing beverages. The method was also reproducible with a coefficient of variation of less than 5% for each analyte. The levels of theophylline, determined by HPLC, were validated by their high correlation to the levels obtained by fluorescence polarization immunoassay. HPLC was used to determine theophylline levels in patients with bronchial asthma. The data revealed that the ratio of 1,3-dimethyluric acid, the major metabolite of theophylline, to theophylline concentration in the plasma was within a narrow range in most patients (0.055 +/- 0.01, n = 66), regardless of the method of theophylline administration or the time of blood sampling. Conversely, this ratio was as low as 0.027 +/- 0.005 in the patient with a long plasma half-life of theophylline. These results suggest that it may be possible to predict the plasma half-life of theophylline for each patient from a single blood sample. This may be useful when planning theophylline administration, especially in patients with abnormal theophylline metabolism.

Polypharmacy and Malnutrition Management of Elderly Perioperative Patients with Cancer: A Systematic Review.

Abstract: Malnutrition, which commonly occurs in perioperative patients with cancer, leads to decreased muscle mass, hypoalbuminemia, and edema, thereby increasing the patient’s risk of various complications. Thus, the nutritional management of perioperative patients with cancer should be focused on to ensure that surgical treatment is safe and effective, postoperative complications are prevented, and mortality is reduced. Pathophysiological and drug-induced factors in elderly patients with cancer are associated with the risk of developing malnutrition. Pathophysiological factors include the effects of tumors, cachexia, and anorexia of aging. Metabolic changes, such as inflammation, excess catabolism, and anabolic resistance in patients with tumor-induced cancer alter the body’s ability to use essential nutrients. Drug-induced factors include the side effects of anticancer drugs and polypharmacy. Drug–drug, drug–disease, drug–nutrient, and drug–food interactions can significantly affect the patient’s nutritional status. Furthermore, malnutrition may affect pharmacokinetics and pharmacodynamics, potentiate drug effects, and cause side effects. This review outlines polypharmacy and malnutrition, the impact of malnutrition on drug efficacy, drug–nutrient and drug–food interactions, and intervention effects on polypharmacy or cancer cachexia in elderly perioperative patients with cancer.

Anticholinergic Load and Nutritional Status in Older Individuals

Abstract: The association between anticholinergic load-based Anticholinergic Risk Scale scores and nutritional status is unclear in Japanese patients. The aim of this study was to establish whether anticholinergic load affects the nutritional status of geriatric patients in convalescent stages. Retrospective longitudinal cohort study. Convalescent rehabilitation wards. Of the 1490 patients aged ≥65 years who were discharged from convalescent rehabilitation wards between July 2010 and October 2018, 908 patients met the eligibility criteria. They were categorized according to the presence or absence of increased anticholinergic load from admission to discharge. Demographic data, laboratory data, the Functional Independence Measure were analyzed between the groups. The primary outcome was Geriatric Nutritional Risk Index (GNRI) at discharge. Multiple linear regression analysis was performed to analyze the relationship between anticholinergic load and GNRI at discharge. Multiple linear regression analysis after adjusting for confounding factors revealed that anticholinergic load was independently and negatively correlated with GNRI at discharge. Particularly, the use of chlorpromazine, hydroxyzine, haloperidol, metoclopramide, risperidone, etc. increased significantly from admission to discharge. Increased anticholinergic load during hospitalization may be a predictor of nutritional status in geriatric patients.

The impact of decreasing potentially inappropriate medications on activities of daily living in a convalescent rehabilitation setting

Abstract: Background Polypharmacy or potentially inappropriate medications negatively affect the functional recovery of rehabilitation. However, limited research exists regarding the effect of decreasing in potentially inappropriate medications use on functional improvement of rehabilitation in geriatric Japanese patients. Objective To elucidate whether decreasing PIM during hospitalization could be a predictor of rehabilitation outcomes among geriatric patients in a convalescent rehabilitation setting. Setting This study was conducted at the convalescent rehabilitation ward in the Hitachinaka General Hospital in Japan. Methods This retrospective observational cohort study included consecutive geriatric patients admitted at the convalescent rehabilitation ward between 2010 and 2018. Participants were divided based on presence or absence of decreasing in potentially inappropriate medications use during hospitalization. A multiple linear regression analysis was performed to analyze whether decreasing potentially inappropriate medications use during hospitalization could be a predictor of Functional Independence Measure-Motor at discharge. Main outcome measures The primary outcome was the Functional Independence Measure-Motor at discharge. Results In total, 569 participants (interquartile range 73–85 years; 33.6% men) were included in the present study. A multiple linear regression analysis of Functional Independence Measure-Motor at discharge, adjusting for confounding factors, revealed that decreasing in potentially inappropriate medications use was independently correlated with Functional Independence Measure-Motor at discharge. In particular, the use of first-generation antihistamines, antipsychotics, benzodiazepines, and non-steroidal anti-inflammatory drugs among potentially inappropriate medications decreased significantly during hospitalization. Conclusion Decreased potentially inappropriate medications use during hospitalization may be a predictor of improvement of rehabilitation outcomes in geriatric patients.

Effect of St. John's wort on the pharmacokinetics of theophylline in healthy volunteers.

Abstract: The objective of this study was to investigate the effect of St. John's wort (SJW, Hypericum perforatum) on the pharmacokinetics of theophylline in healthy volunteers. Twelve healthy Japanese male volunteers participated in this randomized, open-labeled, crossover study. The subjects took an SJW caplet (300 mg) three times a day for 15 days. On day 14, they received a single oral dose of 400 mg of theophylline. They took the same dose of theophylline without SJW treatment on another occasion. Plasma and urine samples were obtained during a 48-hour period after theophylline administration. Theophylline concentrations in plasma and urine, as well as the major metabolites (13U, 1U, 3X) in urine, were measured. SJW caused no significant changes in the pharmacokinetics of theophylline in plasma. SJW administration tended to increase the ratio of 1U/the total amount excreted in urine. However, no changes in the ratio of unchanged theophylline, 13U, and 3X were observed. It is unlikely that the effect of 15 days of treatment with SJW on CYPs is sufficient to cause a change in plasma theophylline concentrations.

Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review

Abstract: The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern The aim was to conduct a systematic literature review of the outcomes of switching between biologics and their biosimilars and identify any evidence gaps A systematic literature search was conducted in PubMed, EMBASE and Cochrane Library from inception to June 2017 Relevant societal meetings were also checked Peer-reviewed studies reporting efficacy and/or safety data on switching between originator and biosimilar products or from one biosimilar to another were selected Studies with fewer than 20 switched patients were excluded Data were extracted on interventions, study population, reason for treatment switching, efficacy outcomes, safety and anti-drug antibodies The systematic literature search identified 63 primary publications covering 57 switching studies The reason for switching was reported as non-medical in 50 studies (23 clinical, 27 observational) Seven studies (all observational) did not report whether the reasons for switching were medical or non-medical In 38 of the 57 studies, fewer than 100 patients were switched Follow-up after switching went beyond 1 year in eight of the 57 studies Of the 57 studies, 33 included statistical analysis of disease activity or patient outcomes; the majority of these studies found no statistically significant differences between groups for main efficacy parameters (based on P < 005 or predefined acceptance ranges), although some studies observed changes for some parameters Most studies reported similar safety profiles between groups There are important evidence gaps around the safety of switching between biologics and their biosimilars Sufficiently powered and appropriately statistically analysed clinical trials and pharmacovigilance studies, with long-term follow-ups and multiple switches, are needed to support decision-making around biosimilar switching