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.

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)

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

scholarly journals Comparative study of pharmacokinetics of two new fluoroquinolones, balofloxacin and grepafloxacin, in elderly subjects.

1996 ◽  
Vol 40 (12) ◽  
pp. 2824-2828 ◽  
Author(s):  
O Kozawa ◽  
T Uematsu ◽  
H Matsuno ◽  
M Niwa ◽  
S Nagashima ◽  
...  
Keyword(s):  
Drug Concentration ◽  
The Elderly ◽  
Plasma Drug Concentration ◽  
Elderly Subjects ◽  
Maximum Plasma ◽  
Plasma Drug ◽  
Urinary Recovery ◽  
Time Curve ◽  
Younger Adults ◽  
Healthy Elderly

Comparative pharmacokinetics and tolerability were studied in healthy elderly volunteers for two new fluoroquinolones, balofloxacin (Q-35) and grepafloxacin (OPC-17116), the main excretion routes being the renal and hepatic routes, respectively. Both agents were well tolerated in elderly subjects. In comparison with previously reported data from healthy younger adults, the absorption of balofloxacin was slightly delayed and urinary excretion was delayed and diminished. As a significant linear correlation was observed between renal clearance of balofloxacin and creatinine clearance, the delayed and diminished urinary recovery was attributed to the reduced renal function of the elderly subjects enrolled in the study. The absorption of grepafloxacin was also delayed, and the maximum plasma drug concentration and area under the plasma drug concentration-time curve were increased in the elderly by 31 and 48%, respectively, over those in younger adults on the basis of dose normalized to body weight. The plasma terminal elimination half-life and urinary recovery remained unchanged. Decreases in distribution volume and total body clearance in the elderly were considered to be the primary factors contributing to these differences.

scholarly journals P0296LAST HIT ‘' INFECTIONS'’ BROUGHT THE END: CHRONIC KIDNEY DISEASE TO RENAL REPLACEMENT TREATMENT

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Feyza Bora ◽  
Emine Asar ◽  
Fatih Yılmaz ◽  
Ümit Çakmak ◽  
Fevzi F Ersoy ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Outpatient Clinic ◽  
Artery Bypass ◽  
Kidney Injury ◽  
The Elderly ◽  
Severe Form ◽  
Vaccination Programs ◽  
Cardiac Decompensation ◽  
Replacement Treatment

Abstract Background and Aims It is evident that Chronic Kidney Disease (CKD) influences the risk of developing AKI (Acute Kidney Injury) and recent studies suggest that CKD patients who experienced an episode of AKI are more likely to progress to end stage renal disease (ESRD) than patients without CKD. AKI-CKD association might originate from common comorbidities associated with both AKI and CKD, such as diabetes and/or hypertension, and concurrent increase in interventions leading to frequent exposure to various nephrotoxins. AKI in the elderly has been shown to increase the risk of progression to CKD to ESRD. AKI is common in critically ill patients, and those patients with the most severe form of AKI, requiring RRT, have a mortality rate of 50–80 %. Patients with an eGFR <45 ml/min per 1.73m2 who experienced an episode of dialysis-requiring AKI were at very high risk for impaired recovery of renal function. Our aim was to determine the reasons that initiate hemodialysis (renal decompensation) in patients with regular follow-up in the low clearance polyclinic without renal replacement treatment (RRT). Method The retrospective study included predialysis CKD patients who had followed up regularly and had undergone RRT in recent 4 years. Data on baseline characteristics and medical history were obtained from patient hospital records. Results Of the 228 patients, 155 (68%) were male and 73 (32%) were female. The mean age was 58 years (45-66). Diabetes Mellitus was the first in the etiology of CKD (26,3 %), the second was unknown (12,7 %), the third was hypertension (11,8 %). 145 patients (63,6%) underwent regular hemodialysis (HD) (62 years, 55-69), 25 patients (11%) began peritoneal dialysis (PD), 58 patients (25%) had renal transplantation. 52 patients underwent HD with renal decompensation, 22 (%42,3) had working arteriovenous fistula (AVF). There was no decompensation in patients with PD or transplantation plan. 34 patients started HD because of infections (65%), 8 patients (15%) after operations (4 was Coronary Artery Bypass Grafting-CABG), 6 patients (%11,5) after coronary angiography, 4 patients (7,5%) with cardiac decompensation. 2 patients died during the hospitalisation for infections. Of 145 HD patients, 89 (%61,4) had AVF. The patients who had renal decompensation were more older 63 (58-70), have lower Hgb 9,7 g/L (9,1-10,7) and albumin 3,5 g/L (3,2-3,9) level (p<0,05). There was no difference in eGFR at the beginning of HD between renal decompensation and other HD patients. 42 patients did not undergo HD at the time we suggested during visits. Of them 9 patients (%21) had renal decompensation (6 infections,3 CABG), 17 patients (%40) had AVF. 3 of them died. The others underwent HD for uremic complications. Conclusion We have shown that infections are as the leading cause of renal decompensation. Most of our patients who started to RRT from our low clearance outpatient clinic have chosen HD for RRT. Prevention of infections via vaccination programs or early diagnosis at regular policlinic or telephone visits, and informing patients adequately about nephrotoxic drugs or the conditions that may cause renal decompensation are among the first tasks of the predialysis outpatient clinic. Transition of CKD patients to RRTs, with proper preparation, neither late nor early- at the most appropriate time- should be among in our goals. This may reduce the cost of ESRD patients.

scholarly journals Effects of Diet Intervention on Body Composition in the Elderly with Chronic Kidney Disease

2017 ◽  
Vol 14 (8) ◽  
pp. 735-740 ◽  
Author(s):  
Kai-Yin Hung ◽  
Terry Ting-Yu Chiou ◽  
Chien-Hsing Wu ◽  
Ying-Chun Liao ◽  
Chian-Ni Chen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Body Composition ◽  
Kidney Disease ◽  
The Elderly ◽  
Diet Intervention

scholarly journals Chronic kidney disease in the elderly: evaluation and management

2014 ◽  
Vol 11 (5) ◽  
pp. 525-535 ◽  
Author(s):  
Mary Mallappallil ◽  
Eli A Friedman ◽  
Barbara G Delano ◽  
Samy I McFarlane ◽  
Moro O Salifu
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
The Elderly

scholarly journals Amiodarone Toxicity Screening: What are the Clinicians Supposed to Tell Patients

2020 ◽  
pp. 1-5
Author(s):  
John D Rozich ◽  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Low Dose ◽  
The Elderly ◽  
Toxicity Screening ◽  
Nonvalvular Atrial Fibrillation ◽  
Routine Testing ◽  
Continued Use

The use of amiodarone in clinical practice continues to be widespread in the setting of nonvalvular atrial fibrillation (NVAF). Use of amiodarone continues especially in the elderly where the drug’s favorable characteristics and outcomes in the setting of chronic kidney disease coupled to its low inherent proarrhythmic profile has ensured its continued use. The present work focuses on the information that clinicians should tell their patients regarding requisite toxicity screening during daily treatment with amiodarone when it is maintained at a low dose of 200 mgs per day or less. Several questions need be answered in pursuit of the fundamental query as to whether routine testing for toxicity should still be advised. Most importantly, has ongoing screening shown to be of any proven value?

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.

scholarly journals Classification of Chronic Kidney Disease in the Elderly: Pitfalls and Errors

2011 ◽  
Vol 119 (s1) ◽  
pp. c2-c4 ◽  
Author(s):  
Christopher G. Winearls ◽  
Richard J. Glassock
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
The Elderly
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