scholarly journals Quantification of CYP3A and Drug Transporters Activity in Healthy Young, Healthy Elderly and Chronic Kidney Disease Elderly Patients by a Microdose Cocktail Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Punyabhorn Rattanacheeworn ◽  
Stephen J Kerr ◽  
Wonngarm Kittanamongkolchai ◽  
Natavudh Townamchai ◽  
Suwasin Udomkarnjananun ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Half Life ◽  
Dabigatran Etexilate ◽  
Organic Anion ◽  
Maximum Plasma ◽  
Cyp3a Activity ◽  
Cancer Resistance ◽  
Healthy Elderly

Background: Ageing and chronic kidney disease (CKD) affect pharmacokinetic (PK) parameters. Since mechanisms are related and remain unclear, cytochrome P450 (CYP) 3A and drug transporter activities were investigated in the elderly with or without CKD and compared to healthy adults using a microdose cocktail.Methods: Healthy young participants (n = 20), healthy elderly participants (n = 16) and elderly patients with CKD (n = 17) received, in study period 1, a single dose of microdose cocktail probe containing 30 µg midazolam, 750 µg dabigatran etexilate, 100 µg atorvastatin, 10 µg pitavastatin, and 50 µg rosuvastatin. After a 14-day wash-out period, healthy young participants continued to study period 2 with the microdose cocktail plus rifampicin. PK parameters including area under the plasma concentration-time curve (AUC), maximum plasma drug concentration (Cmax), and half-life were estimated before making pairwise comparisons of geometric mean ratios (GMR) between groups.Results: AUC and Cmax GMR (95% confidence interval; CI) of midazolam, a CYP3A probe substrate, were increased 2.30 (1.70–3.09) and 2.90 (2.16–3.88) fold in healthy elderly and elderly patients with CKD, respectively, together with a prolonged half-life. AUC and Cmax GMR (95%CI) of atorvastatin, another CYP3A substrate, was increased 2.14 (1.52–3.02) fold in healthy elderly and 4.15 (2.98–5.79) fold in elderly patients with CKD, indicating decreased CYP3A activity related to ageing. Associated AUC changes in the probe drug whose activity could be modified by intestinal P-glycoprotein (P-gp) activity, dabigatran etexilate, were observed in patients with CKD. However, whether the activity of pitavastatin and rosuvastatin is modified by organic anion transporting polypeptide 1B (OATP1B) and of breast cancer resistance protein (BCRP), respectively, in elderly participants with or without CKD was inconclusive.Conclusions: CYP3A activity is reduced in ageing. Intestinal P-gp function might be affected by CKD, but further confirmation appears warranted.Clinical Trial Registration:http://www.thaiclinicaltrials.org/ (TCTR 20180312002 registered on March 07, 2018)

scholarly journals Quantification of CYP3A and drug transporters activity in healthy young, healthy elderly and chronic kidney disease elderly patients by a microdose cocktail approach

2021 ◽  
Author(s):  
Punyabhorn Rattanacheeworn ◽  
Stephen Kerr ◽  
Wonngarm Kittanamongkolchai ◽  
Natavudh Townamchai ◽  
Suwasin Udomkarnjananun ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Half Life ◽  
Dabigatran Etexilate ◽  
Geometric Mean ◽  
The Elderly ◽  
Maximum Plasma ◽  
Cancer Resistance ◽  
Time Curve ◽  
Healthy Elderly

Aims: Ageing and chronic kidney disease (CKD) are known to affect pharmacokinetics (PK) parameters. Since mechanisms are related and remain unclear, cytochrome P450 (CYP)3A and drug transporter activity were investigated in the elderly with or without CKD and compared to healthy adults using a microdose cocktail. Methods: Healthy young volunteers (n = 20), healthy elderly volunteers (n = 16) and elderly with CKD (n = 17) received a single dose of microdose cocktail probe containing 30 µg midazolam, 750 µg dabigatran etexilate, 100 µg atorvastatin, 10 µg pitavastatin, and 50 µg rosuvastatin. After a 14-day washout period, healthy young volunteers continued to study period 2 with the microdose cocktail plus rifampicin. PK parameters including area under the concentration-time curve (AUC), maximum plasma drug concentration (Cmax) and half-life were estimated before making pairwise comparisons of geometric mean ratios between groups. Results: AUC and Cmax of midazolam, a CYP3A probe substrate, were increased 2.30 and 2.90 fold in healthy elderly and elderly with CKD, respectively, leading to a prolonged half-life. AUC and Cmax of atorvastatin, another CYP3A4 probe substrate, was increased 2.14 fold in healthy elderly and 4.15 fold in elderly with CKD, indicating decreased CYP3A4 activity related to ageing. Association with PK changes in probe drugs representing activity of OATP1B1, intestinal P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) transporters was noticed, but were inconclusive. Conclusions: CYP3A activity is reduced in ageing. There is a trend in changes of OATP1B1, P-gp, and BCRP activity measured by microdose cocktail probe drugs.

Dabigatran etexilate: appropriate use in patients with chronic kidney disease and in the elderly patients

2017 ◽  
Vol 12 (4) ◽  
pp. 425-435 ◽  
Author(s):  
Mauro Molteni ◽  
Mario Bo ◽  
Giovanni Di Minno ◽  
Giuseppe Di Pasquale ◽  
Simonetta Genovesi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Dabigatran Etexilate ◽  
The Elderly ◽  
Appropriate Use

Risk factors for high fall risk in elderly patients with chronic kidney disease

2021 ◽  
Author(s):  
Cihan Heybeli ◽  
Rumeyza Kazancioglu ◽  
Lee Smith ◽  
Nicola Veronese ◽  
Pinar Soysal
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Fall Risk

FEATURES OF CHRONIC KIDNEY DISEASE IN ELDERLY PATIENTS

2020 ◽  
pp. 113-120
Author(s):  
О. Н. Курочкина
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Clinical Situation ◽  
Chronic Glomerulonephritis ◽  
Hypertensive Nephropathy ◽  
Number Of Patients ◽  
Rate Of Decline ◽  
People Group ◽  
Group 1

Изучены особенности течения хронической болезни почек (ХБП) у пожилых пациентов на основании анализа регистра ХБП за 2015-2018 гг. В регистре 484 пациента, из них 231 (47,7%) мужчина, 253 (52,3%) женщины, средний возраст - 58,8±15,8 года. Пациенты были разделены на три группы: 1-я - 218 человек до 59 лет; 2-я - 207 человек 60-74 лет; 3-я - 59 человек 75 лет и старше. В 1-й группе ведущей причиной ХБП явился хронический гломерулонефрит -27,1%, во 2-й - хронический тубулоинтерстициальный нефрит (ТИН) - 21,7%, диабетическая нефропатия (ДН) - 20,8% и гипертоническая нефропатия - 15,9%; в 3-й - ТИН (27,1%), хронический пиелонефрит (ПН) - 15,9% и ДН (13,6%). С возрастом увеличивалась частота встречаемости ТИН ( р <0,1), ПН ( р <0,05), ишемической болезни почек ( р <0,05), подагрической нефропатии ( р <0,1). Среднее снижение СКФ - 3,99 мл/мин на 1,73 мза год наблюдения. Темп снижения СКФ в 1-й группе - 3,36±1,8 мл/мин на 1,73 мза год, во 2-й - 2,43±1,2 ( р <0,001 между 1-йи 2-й группой), в 3-й - 1,82±1,1 мл/мин на 1,73 мза год. Наблюдали отрицательную корреляцию с возрастом ( р <0,05). Формирование регистра больных с ХБП позволяет знать количество больных и причины ХБП у пациентов пожилого и старческого возраста, оценивать клиническую ситуацию, темпы снижения СКФ и выбирать лечебную тактику у этих пациентов. The purpose of the work is to study the characteristics of the course of chronic kidney disease in elderly patients based on the analysis of the register of chronic kidney disease (CKD) for 2015-2018. in the Department of Nephrology, the Komi Republican Clinical Hospital. There are 484 patients in the register, of whom 231 are men (47,7%), 253 women (52,3%). The average age is 58,8±15,8 years old. The patients were divided into 3 groups: persons under the age of 59 years old - 218 people (group 1); from 60 to 74 years old - 207 people (group 2); and over 75 years old - 59 people (group 3). Most patients are between the ages of 60 and 69 years old. In the 1 group, the chronic glomerulonephritis is the leading cause of CKD - 27,1%; in the 2 group - the chronic tubulo-interstitial nephritis (TIN) - 21,7%, the diabetic nephropathy (DN) - 20,8% and the hypertensive nephropathy - 15,9%; in the 3 group - TIN (27,1%), the chronic pyelonephritis (PN) (15,9%) and DN (13,6%). With increasing age, the incidence of TIN ( p <0,1), MO ( p <0,05), coronary kidney disease (IBP) ( p <0,05), gouty nephropathy ( p <0,1) were raised. The average reduction in GFR is 3,99 ml/min/1,73 m per year of observation. The rate of decline in GFR in the 1st group is 3,36±1,8 ml/min/1,73 m per year, in the 2 - 2,43±1,2 ( p <0,001 between group 1 and 2), in the 3 group - 1,82±1,1; with aging the negative correlation was observed ( p <0,05). 39 patients received hemodialysis, including: in the 1 group - 20 people (9%), in the 2 group - 18 (8,7%), in the 3 group - 1 patient (1,7%). Making the register of the patients with CKD allows us to know the number of patients and the causes of CKD among the patients of elderly and senile ages, to assess the clinical situation, the rate of decline in GFR and treatment tactics in these patients.

scholarly journals Treatment plans and outcomes in elderly patients reaching advanced chronic kidney disease

2018 ◽  
Vol 33 (12) ◽  
pp. 2182-2191 ◽  
Author(s):  
Olivier Moranne ◽  
Coraline Fafin ◽  
Sophie Roche ◽  
Maud Francois ◽  
Vincent Allot ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Advanced Chronic Kidney Disease ◽  
Treatment Plans

scholarly journals MEDICATION BURDEN AND INAPPROPRIATE PRESCRIPTION RISK AMONG ELDERLY WITH ADVANCED CHRONIC KIDNEY DISEASE

2019 ◽  
Author(s):  
Clarisse Roux-Marson ◽  
Jean-Baptiste Baranski ◽  
Coraline Fafin ◽  
Guillaume Extermann ◽  
Cecile Vigneau ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Healthcare Providers ◽  
Antihypertensive Agents ◽  
The Elderly ◽  
Anticholinergic Drugs ◽  
Cross Sectional ◽  
French Study ◽  
Sectional Analysis

Abstract Background Elderly patients with chronic kidney disease (CKD) frequently present comorbidities that put them at risk of polypharmacy and medication-related problems. This study aims to describe the overall medication profile of patients aged ≥ 75 years with advanced CKD from a multicenter French study and specifically the renally (RIMs) and potentially inappropriate-for-the-elderly medications (PIMs) that they take. Methods This is a cross-sectional analysis of medication profiles of individuals aged ≥ 75 years with eGFR < 20 ml/min/1.73m2 followed by a nephrologist, who collected their active prescriptions at the study inclusion visit. Medication profiles were analyzed according to route of administration, therapeutic classification, and their potential inappropriateness for these patients, according to Beers' criteria. Results We collected 5196 individual medication prescriptions for 556 patients, for a median of 9 daily medications [7-11]. Antihypertensive agents, antithrombotics, and antianemics were the classes most frequently prescribed. Moreover, 88% of patients had at least 1 medication classified as a RIM, and 21% of those were contraindicated drugs. At least 1 PIM was taken by 68.9%. The prescriptions most frequently requiring reassessment due to potential adverse effects were for proton pump inhibitors and allopurinol. The PIMs for which deprescription is especially important in this population are rilmenidine, long-term benzodiazepines, and anticholinergic drugs such as hydroxyzine. Conclusion We showed potential drug-related problems in elderly patients with advanced CKD. Healthcare providers must reassess each medication prescribed for this population, particularly the specific medications identified here.

Relationship between renal biopsy and renal survival in elderly patients with chronic kidney disease: A propensity score matching approach

2020 ◽  
Author(s):  
Xiaowei Lou ◽  
Shizhu Yuan ◽  
Wei Shen ◽  
Yueming Liu ◽  
Juan Jin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Renal Biopsy ◽  
Cox Regression ◽  
Renal Survival ◽  
Aged Patients ◽  
Renal Outcomes ◽  
Propensity Matching

Abstract Background The effect of renal biopsy on the prognosis of elderly patients with chronic kidney disease remains unclear. Thus, in this study, we aimed to evaluate the relationship between renal biopsy and renal survival in this population.Methods In this multi-centre retrospective study, the baseline characteristics among three groups were balanced by propensity matching. All patients were divided into three groups according to age and renal biopsy. The clinicopathological features at biopsy and renal outcomes during the follow-up were collected and analysed. Renal outcomes were defined as estimated glomerular filtration rate < 15 mL/min/1.73 m2, dialysis, renal transplantation, or death. The prognostic effects of renal biopsy were evaluated using Cox regression models. Results A total of 1313 patients were identified. After propensity matching, 390 patients were selected and divided into three groups. After a total follow-up period of 55 months, 20 (13.3%) patients (47.6% group 1 vs 7.41% group 2 vs 39.1% group 3) reached renal outcomes. No significant differences were found in renal outcomes among aged patients whether they underwent renal biopsy or not. Cox regression analysis revealed risk factors in aged patients including low albumin and high levels of proteinuria and serum creatinine (P < 0.05). Platelet count was significant only in aged patients who underwent renal biopsy (hazard ratio: 0.642, P < 0.05). Conclusion In conclusion, renal biopsy in the elderly has not shown benefits in terms of renal survival, conservative treatment appears to be a viable therapeutic option in the management of those people.

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