A multiple dose pharmacokinetic and tolerance study of once daily 200 mg sustained-release flurbiprofen capsules in young and very elderly patients

Background- Among the gliptins, vildagliptin is the only therapy requiring twice-daily dosing and thus adversely impacts patient adherence. To reduce dosing frequency, we developed a once-daily sustained-release (SR) vildagliptin 100 mg tablet formulation with potential to furnish comparable dipeptidyl peptidase-4 (DPP-4) inhibition coverage to the conventional twice-daily regimen. Objective- The current study compares the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of investigational once-daily SR vildagliptin 100 mg tablet formulation with the twice-daily dosage of marketed product, Galvus® in healthy Indian adult males after single and multiple-dose administration. Methods- Single and multiple-dose PK-PD assessment was conducted in separate clinical studies enrolling thirty-six healthy subjects under fed-condition. Each study was a randomized, open-label, two treatment, two-period, crossover design. Drug plasma concentrations were quantified by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. DPP-4 inhibition was estimated in the fluorescence-based assay. PK parameters were calculated from the plasma concentration-time curve employing Phoenix® WinNonlin® software. Formulation safety was evaluated by monitoring adverse events. Results- SR vildagliptin 100 mg tablet resulted in peak-less, nearly steady drug concentration-time profile. Thus, its mean PK characteristics after single [Cmax (147.7), AUC(0-24) (1645.04), Tmax (5.29 hr), t1/2 (4.61 hr)] and multiple-dose [Cmaxss (163.59), AUCss (0-24) (1815.36), and Tmaxss (4.65 hrs), t1/2ss (3.71 hr)] administrations were significantly distinct from the Galvus® twice-daily regimen. SR vildagliptin 100 mg tablet demonstrated more than 80% DPP-4 inhibition profile for approximately 23 hrs in both the studies which was comparable to Galvus® twice-daily regimen. Conclusions- Investigational SR vildagliptin 100 mg tablet formulation was found to be safe and well-tolerated. Its ability to provide nearly 80% DPP-4 inhibition coverage over 23 hrs post-dose may reduce the additional pill burden in patients on conventional twice-daily regimen.

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Direct oral anticoagulants for prevention of stroke and other cardiovascular outcomes in patients aged 80 years or older with atrial fibrillation

Clinical pharmacology and therapy ◽

10.32756/0869-5490-2021-1-16-23 ◽

2021 ◽

Vol 30 (1) ◽

pp. 16-23

Author(s):

S. Moiseev

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Elderly Patients ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Very Elderly ◽

Once Daily ◽

Increased Risk ◽

Reduced Kidney Function

Over the last decade, the number of people aged 80 years or over in Russia increased by 41% up to 5.7 mln. At least 10% of these individuals develop atrial fibrillation (AF). Treatment of rhythm disorders in the very elderly patients is challenging due to the high occurrence of comorbidities, including cognitive dysfunction, changes in the pharmacokinetics of drugs as a result of reduced kidney function, increased risk of interaction of drugs. The very elderly patients with AF have a higher risk of ischemic stroke and other cardiovasculat outcomes, including myocardial infarction, and should be treated with oral anticoagulants. The results of randomized controlled trials and prospective and retrospective observational studies suggest that in patients aged 80 years or older with non-valvular AF direct oral anticoagulants (DOAC) are at least as effective as vitamin K antagonists for prevention of ischemic stroke and are associated with a lower risk of intracerebral haemorrhage. The use of DOAC (once daily rivaroxaban in particular) impoves compliance to anticoagulation in the very elderly patients with non-valvular AF.

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Features of diabetes mellitus in very elderly patients

Medical alphabet ◽

10.33667/2078-5631-2019-1-9(384)-13-19 ◽

2019 ◽

Vol 1 (9) ◽

pp. 13-19

Author(s):

S. V. Topolyanskaya ◽

T. M. Kolontai ◽

O. N. Vaculenko ◽

L. I. Dvoretski

Keyword(s):

Diabetes Mellitus ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Elderly Patients ◽

Very Elderly ◽

Younger Patients ◽

Patients With Diabetes ◽

Artery Disease

Modern concepts about features of diabetes mellitus in very elderly patients are described in the article. Special attention to the therapeutic methods of management of very elderly patients with diabetes mellitus has been devoted. The results of diabetes mellitus study in patients with coronary artery disease older than 75 years in comparison with younger patients are presented.

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CARDIOVASCULAR DISEASE IN VERY ELDERLY PATIENTS HOSPITALIZED IN A DISTRICT HOSPITAL

Journal of Hypertension ◽

10.1097/01.hjh.0000539706.81239.05 ◽

2018 ◽

Vol 36 (Supplement 1) ◽

pp. e249

Author(s):

M. Mellado-Ferreiro ◽

V. Jarne-Betrán ◽

M. Arteaga-Mazuelas ◽

A. Redondo-Arriazu ◽

L. Urbina-Soto

Keyword(s):

Cardiovascular Disease ◽

Elderly Patients ◽

District Hospital ◽

Very Elderly

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THE ASSOCIATION OF BODY MASS INDEX AND ANEMIA ON REVASCULARIZATION OUTCOMES IN VERY ELDERLY PATIENTS PRESENTING WITH ACUTE MYOCARDIAL INFARCTION

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(21)01451-0 ◽

2021 ◽

Vol 77 (18) ◽

pp. 92

Author(s):

Derek Phan ◽

Ara Rostomian ◽

Ming-Sum Lee ◽

Naing Moore ◽

Prakash Mansukhani ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Body Mass Index ◽

Elderly Patients ◽

Body Mass ◽

Very Elderly

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Determinants of In-Hospital Mortality in Elderly Patients Aged 80 Years or above with Acute Heart Failure: A Retrospective Cohort Study at a Single Rural Hospital

Journal of Clinical Medicine ◽

10.3390/jcm10071468 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1468

Author(s):

Yusuke Watanabe ◽

Kazuko Tajiri ◽

Hiroyuki Nagata ◽

Masayuki Kojima

Keyword(s):

Heart Failure ◽

Regression Analysis ◽

Elderly Patients ◽

Hospital Mortality ◽

Acute Heart Failure ◽

Stepwise Regression ◽

Stepwise Regression Analysis ◽

Antibiotic Administration ◽

Very Elderly ◽

Survivor Group

Heart failure is one of the leading causes of mortality worldwide. Several predictive risk scores and factors associated with in-hospital mortality have been reported for acute heart failure. However, only a few studies have examined the predictors in elderly patients. This study investigated determinants of in-hospital mortality in elderly patients with acute heart failure, aged 80 years or above, by evaluating the serum sodium, blood urea nitrogen, age and serum albumin, systolic blood pressure and natriuretic peptide levels (SOB-ASAP) score. We reviewed the medical records of 106 consecutive patients retrospectively and classified them into the survivor group (n = 83) and the non-survivor group (n = 23) based on the in-hospital mortality. Patient characteristics at admission and during hospitalization were compared between the two groups. Multivariate stepwise regression analysis was used to evaluate the in-hospital mortality. The SOB-ASAP score was significantly better in the survivor group than in the non-survivor group. Multivariate stepwise regression analysis revealed that a poor SOB-ASAP score, oral phosphodiesterase 3 inhibitor use, and requirement of early intravenous antibiotic administration were associated with in-hospital mortality in very elderly patients with acute heart failure. Severe clinical status might predict outcomes in very elderly patients.

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Ventilatory defects and treatable traits in very elderly patients

Science Progress ◽

10.1177/00368504211013171 ◽

2021 ◽

Vol 104 (2) ◽

pp. 003685042110131

Author(s):

João Gaspar-Marques ◽

Teresa Palmeiro ◽

Iolanda Caires ◽

Paula Leiria Pinto ◽

Nuno Neuparth ◽

...

Keyword(s):

Cognitive Impairment ◽

Elderly Patients ◽

Elderly Care ◽

Airflow Limitation ◽

The Novel ◽

Z Score ◽

Very Elderly ◽

Chronic Respiratory Diseases ◽

Novel Association ◽

Peripheral Pulse

Though the approach used to classify chronic respiratory diseases is changing to a treatable-traits (TT) approach, data regarding very elderly patients is lacking. The objectives of this study were to assess TT frequency in very elderly patients and to study the link between extrapulmonary TT and ventilatory defects. Individuals (≥75 years) residing in elderly care centres answered a standardised questionnaire, underwent spirometry, atopy and fractional exhaled nitric oxide assessments and had their blood pressure and peripheral pulse oximetry measured. Pulmonary, extrapulmonary and behavioural TT were evaluated. Outcome variables were an airflow limitation (post-bronchodilator z-score FEV1/FVC<−1.64) and a restrictive spirometry pattern (z-score FEV1/FVC ≥ +1.64 and z-score FVC<−1.64). Seventy-two percent of the individuals who took part in the study ( n = 234) were women, and the median age of participants was 86 (IQR: 7.4). At least one pulmonary TT was identified in 105 (44.9%) individuals. The most frequent extrapulmonary TTs were: persistent systemic inflammation (47.0%), anaemia (34.4%), depression (32.5%) and obesity (27.4). Airflow limitation was exclusively associated with smoking (OR 5.03; 95% CI 1.56–16.22). A restrictive spirometry pattern was associated with cognitive impairment (OR: 3.89; 95% CI: 1.55–9.79). A high frequency of various TTs was found. The novel association between a restrictive spirometry pattern and cognitive impairment highlights the urgency of clinical research on this vulnerable age group.

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Non-steroidal anti-inflammatory drugs in the pharmacological management of osteoarthritis in the very old: prescribe or proscribe?

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x211022149 ◽

2021 ◽

Vol 13 ◽

pp. 1759720X2110221

Author(s):

Christian Cadet ◽

Emmanuel Maheu ◽

Keyword(s):

Elderly Patients ◽

Excess Mortality ◽

Absolute Risk ◽

Accurate Information ◽

Plain Language ◽

Very Elderly ◽

Old Patients ◽

Very Old ◽

Inflammatory Drugs ◽

Anti Inflammatory

Osteoarthritis (OA) is the most common form of arthritis worldwide, and ranges in the top 5–10 most disabling diseases. Contrary to common opinion, this disease is severe, often symptomatic, and may lead to loss of mobility and independence, as well as being responsible for increased frailty and excess mortality [standardized ratio: 1.55 (95% confidence interval, CI: 1.41–1.70)]. The incidence of OA increases dramatically with age in an increasingly ageing world. Therefore, practitioners involved in the management of OA often have to manage very old patients, aged 75–80 years and above, as part of their daily practice. Treatment options are limited. In addition to education and physical treatments, which are at the forefront of all treatment recommendations but require a low level of symptoms to be implemented, many pharmacological options are proposed. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used as a second-line treatment but with great caution. However, the precise incidence of cardiovascular, renal, and gastrointestinal adverse events in very elderly patients is unclear. All of these risks are increased in the elderly. The relative risks can be extrapolated from various studies. However, what is the absolute risk according to age categorization? The answer to this question is important because NSAIDs should be used in very elderly patients with OA only if full information has been provided and the decision to prescribe this treatment is shared between the patient and their doctor. This article reviews the risks and currently available recommendations, and proposes practical options and warnings to allow for a responsible and limited use of NSAIDs in the very old. Plain language summary NSAIDS in the very Old : Prescribe or Proscribe? Osteoarthritis (OA) in the very old is a serious disease leading to loss of independence, frailty, and excess mortality. Quantitative data from clinical trials and population-based observational studies on the risk of NSAID-related side effects allow the prescriber to provide more accurate information to each patient. If there is no contraindication, the decision to initiate NSAID therapy in a very old OA patient should be made in a shared manner, with the patient fully informed of the risks.

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