Pharmacokinetics of lenalidomide in subjects with various degrees of renal function

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2520-2520
Author(s):  
N. Chen ◽  
H. Lau ◽  
L. Kong ◽  
J. Zeldis ◽  
R. Knight ◽  
...  
Keyword(s):  
Renal Function ◽  
Creatinine Clearance ◽  
Strongly Correlated ◽  
Pooled Data ◽  
Safety Parameters ◽  
Immunomodulatory Drug ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage ◽  
Initial Starting

2520 Background: Lenalidomide is a novel oral immunomodulatory drug approved for treating myelodysplastic syndrome (MDS) and multiple myeloma (MM). As unchanged lenalidomide is eliminated predominantly by urinary excretion, the present study investigated the effect of renal impairment (RI) on pharmacokinetics (PK) of lenalidomide. Results were used to refine initial dosing recommendations based on a subject’s estimated creatinine clearance. Methods: The study was conducted at 3 clinical centers. Thirty male and female subjects aged 39–76 years were stratified into 5 groups based on their creatinine clearance (CLCr) values: normal renal function (NRF) (CLCr > 80 mL/min; N = 7), mild RI (50 = CLCr = 80 mL/min; N = 5), moderate RI (30 = CLCr < 50 mL/min; N = 6), severe RI (CLCr < 30 mL/min, but not on dialysis; N = 6), and end stage renal disease (ESRD, requiring dialysis; N = 6). Subjects with NRF, mild, moderate or severe RI received a single 25-mg oral dose of lenalidomide. Subjects with ESRD received 2 single 25 mg doses which were separated by 7–10 days: one dose on a non-dialysis day and the other dose 3 hours before a 4-hour haemodialysis. Assessments included PK and safety parameters. Results: All subjects completed the study. Total and renal clearance of lenalidomide were strongly correlated with CLCr (R > 0.9, p < 0.01). As a result, AUC8 increased with decreasing CLCr. The mean difference in AUC8 between NRF and mild RI was < 20%. Compared with the pooled data from NRF and mild RI groups, mean AUC8 increased approximately 140% in moderate RI, 240% in severe RI, and 360% in ESRD (off dialysis). There was no correlation between Cmax or Tmax and CLCr. Approximately 10% of the dose was recovered in the dialysate of subjects with ESRD. Protein binding of lenalidomide was not markedly affected by RI (∼35 - 44%). The drug was well tolerated. On the basis of these data, recommendations for initial starting doses were made ( Table below). Conclusions: Lenalidomide dosage adjustment should be considered for patients with CLCr < 50 mL/min. [Table: see text] No significant financial relationships to disclose.

scholarly journals Single-Center Investigation of the Pharmacokinetics of WCK 4282 (Cefepime-Tazobactam Combination) in Renal Impairment

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Richard A. Preston ◽  
Grigor Mamikonyan ◽  
Mushtaque Mastim ◽  
Dyal Garg ◽  
Christopher J. Kemper ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Bacterial Infections ◽  
Severe Renal Impairment ◽  
Multidrug Resistant ◽  
Time Curve ◽  
Healthy Control ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage

ABSTRACT WCK 4282 is a combination product of cefepime (FEP) and tazobactam (TAZ) in a 1:1 ratio currently under development for the treatment of multidrug-resistant Gram-negative bacterial infections. We investigated the effect of renal impairment on the pharmacokinetics (PK) and safety of WCK 4282 in 48 subjects with various degrees of renal function. Subjects were categorized on the basis of their Cockcroft-Gault equation-estimated creatinine clearance (CLCR). We enrolled 6 subjects each into those with mild (CLCR, 60 to <90 ml/min), moderate (CLCR, 30 to <60 ml/min), or severe (CLCR, <30 ml/min) renal impairment and those with end-stage renal disease (ESRD) requiring hemodialysis and 24 healthy control subjects (CLCR, ≥90 ml/min). Healthy subjects and subjects with mild and moderate renal impairment received a single 90-min infusion of 4 g of WCK 4282 (2 g FEP and 2 g TAZ). Subjects with severe renal impairment and ESRD received 2 g of WCK 4282 (1 g FEP and 1 g TAZ) over 90 min. The plasma exposure of FEP-TAZ increased as renal function decreased. In subjects with mild, moderate, and severe renal impairment and ESRD, the mean exposure (area under the plasma concentration versus time curve from time zero extrapolated to infinity) of FEP and TAZ increased by 1.3- and 1.2-fold, 2.3- and 2.3-fold, 4.7- and 4.0-fold, and 8.5- and 11.6-fold, respectively. The urinary recovery of FEP and TAZ decreased with increasing renal impairment. There were no adverse events reported during the study. The findings suggest that dose adjustments for WCK 4282 will be required according to the degree of renal impairment. A single infusion of WCK 4282 was found to be safe and well tolerated in subjects with normal and impaired renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT02709382.)

Estimation of Total Creatinine Clearance is Unreliable in Children on Peritoneal Dialysis

1996 ◽  
Vol 16 (1) ◽  
pp. 73-77 ◽  
Author(s):  
Christoph Aufricht ◽  
Erwin Kitzmüller ◽  
Maria-Anna Lothaller ◽  
Thomas Müller ◽  
Robert Birnbacher ◽  
...  
Keyword(s):  
Renal Function ◽  
Peritoneal Dialysis ◽  
Creatinine Clearance ◽  
Residual Renal Function ◽  
Mean Value ◽  
Schwartz Formula ◽  
Dialysis Unit ◽  
Serial Measurement ◽  
The Mean ◽  
Stage Renal Disease

Objective To test the reliability of creatinine clearance in children on peritoneal dialysis (PD). Design Longitudinal, case-controlled. Setting Routine clinic visits at the pediatric dialysis unit of the Universitätskinderklinik of Vienna. Patients: Eleven children (2 -13 years, 10 -55 kg) with end-stage renal disease on PD. Interventions Creatinine clearance (CCr) was determined by measuring creatinine excretion (ECr) over 24 hours in both dialysate and urine. Each child had three to five separate measurements of their CCr. At the same time we also calculated the schwartz formula clearance from the patient's height and serum creatinine, using a modified correlate. Main Outcome Measures Reliability of CCr was assessed by two approaches. First, we compared each serial measurement with the mean value for each patient and thereby assessed the “intramethodical” variability. Second, we compared each CCr with the simultaneous formula clearance and assessed the “intermethodical” disagreement. Results Twenty-seven percent of the measurements of CCr were classified as unreliable based on a comparison with the mean value for each patient. Reliability was closely correlated with residual renal function (p < 0.01); only 12% of the measurements in the an uric patients were classified as unreliable (vs 31% in the patients with residual renal function). The simultaneous formula clearance was less variable than the CCr. The formula clearance had a sensitivity of 93% and a specificity of 60% for detecting unreliable values of CCr. Conclusion Estimation of total CCr is unreliable in pediatric patients on PD. A simultaneous formula clearance can be used to detect which values are unreliable.

scholarly journals Pharmacokinetics and Safety of Omadacycline in Subjects with Impaired Renal Function

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Jolene K. Berg ◽  
Evan Tzanis ◽  
Lynne Garrity-Ryan ◽  
Stephen Bai ◽  
Surya Chitra ◽  
...  
Keyword(s):  
Renal Function ◽  
Healthy Subjects ◽  
Impaired Renal Function ◽  
Phase 1 ◽  
Time Curve ◽  
Concentration Time ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage ◽  
Drug Resistant Strains

ABSTRACT Many antibiotics require dose adjustments in patients with renal impairment and/or in those undergoing hemodialysis. Omadacycline, the first aminomethylcycline antibiotic in late-stage clinical development, displays activity against a broad spectrum of bacterial pathogens, including drug-resistant strains. Data from completed phase 3 studies of omadacycline for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) showed intravenous (i.v.) to once-daily oral omadacycline to be clinically effective and well tolerated. To determine if the dosing of omadacycline should be adjusted in patients with impaired renal function, a phase 1 study examining the pharmacokinetics (PK) and safety of i.v. omadacycline (100 mg) was conducted in subjects with end-stage renal disease (ESRD) on stable hemodialysis (n = 8) and in matched healthy subjects (n = 8). i.v. administration of omadacycline produced similar plasma concentration-time profiles in subjects with ESRD and healthy subjects. Further, in subjects with ESRD, similar values of the PK parameters were observed when omadacycline was administered i.v. after or before dialysis. The mean area under the concentration-time curve from time zero extrapolated to infinity in plasma was 10.30 μg · h/ml when omadacycline was administered to ESRD subjects after dialysis, 10.20 μg · h/ml when omadacycline was administered to ESRD subjects before dialysis, and 9.76 μg · h/ml when omadacycline was administered to healthy subjects. The mean maximum observed concentration of omadacycline in plasma in ESRD subjects was 1.88 μg/ml when it was administered after dialysis and 2.33 μg/ml when it was administered before dialysis, and in healthy subjects it was 1.92 μg/ml. The 100-mg i.v. dose of omadacycline was generally safe and well tolerated in both ESRD and healthy subjects. This study demonstrates that no dose adjustment is necessary for omadacycline in patients with impaired renal function or on days when patients are receiving hemodialysis.

Oral and Maxillofacial Manifestations of Mineral and Bone Disorders Associated with Chronic Renal Failure

2017 ◽  
Vol 68 (6) ◽  
pp. 1325-1328
Author(s):  
Andrada Raluca Doscas ◽  
Mihail Balan ◽  
Mihai Liviu Ciofu ◽  
Doriana Agop Forna ◽  
Marius Cristian Martu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Renal Function ◽  
Chronic Renal Failure ◽  
Health Concern ◽  
Oral Manifestations ◽  
End Stage Renal Failure ◽  
Brown Tumors ◽  
The Mean ◽  
End Stage

Chronic kidney disease (CKD) is a multifactorial syndrome and a global health concern. As renal function declines, there is a progressive deterioration of mineral homeostasis. Starting from stage 3 of CKD oral manifestations of mineral disorders can occasionally appear and become more frequent and evident in stage 5. We retrospectively analysed 43 patients diagnosed with end stage renal failure undergoing dialysis, hospitalized in our clinic for different oral and maxillofacial pathologies. The mean dialysis period was 5.43 years. Radiographic alterations afecting the jaws were found in all patients. The most common feature was partial or total loss of lamina dura, followed by alterations of the bony trabeculae. 9 patients presented brown tumors which are considered the final stage of secondary hyperparathyroidism associated with renal failure.

MO403ACUTE KIDNEY INJURY IN ELDERLY: EPIDEMIOLOGICAL, CLINICAL AND ETIOLOGICAL FEATURES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Mouna Malki abidi ◽  
Rajaa Aoudia ◽  
Soumaya Chargui ◽  
Imen Gorsane ◽  
Mouna Jerbi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Injury ◽  
The Elderly ◽  
Major Interest ◽  
The Mean ◽  
Renal Aging ◽  
End Stage ◽  
Iatrogenic Origin

Abstract Background and Aims Acute kidney injury (AKI) is common in the elderly due to physiologic renal aging and underlying pathologies. Few studies focused on AKI in Tunisian elderly. The aim of our study was to highlight the epidemiological, clinical, etiological, therapeutic, and progressive characteristics of AKI in elderly. Method We conducted a descriptive retrospective study of AKI in patients admitted to our department over a period of 04 years from 01/01/2014 to 31/12/2017. Results We collected 40 patients including 25 women and 15 men with a sex ratio of 1.66. The mean age was 74 [65-87] years. We noted the presence of pre-existing chronic kidney disease in 58% of cases, diabetes in 50% of cases and hypertension in 73% of cases. Polypharmacy was found in 40% of cases. AKI was symptomatic in 80% of cases and found on a routine check-up in 20% of cases. Mean creatinine was 612+/-334 µmol/l. AKI was pre-renal in 37% and parenchymal in 63% of cases. Iatrogenic origin was found in 33% of cases. Renal biopsy was performed for diagnostic purposes in 6 cases. Haemodialysis was necessary in 50% of cases. Etiopathogenic treatment was initiated in 73% of cases. Intra-hospital mortality was 10%, recovery of renal function (RF) was partial in 40 % of cases and total in 20 % of cases. Follow-up time was 16 +/- 23.2 months. And at the last news, recovery of renal function (RF) was partial in 7 cases and total in 10 cases, 6 patients kept a chronic renal failure (CRF), among them 3 cases had and end-stage of CRF. Conclusion AKI is a frequent pathology in the elderly and its severity is linked to mortality and the transition to chronicity. Iatrogenic causes are frequent and preventable in this population, hence the major interest of prevention.

scholarly journals Outcomes of Chronic Hemodialysis Patients in the Intensive Care Unit

2013 ◽  
Vol 2013 ◽  
pp. 1-7
Author(s):  
Melanie Chan ◽  
Marlies Ostermann
Keyword(s):  
Intensive Care Unit ◽  
Renal Function ◽  
Intensive Care ◽  
Kidney Injury ◽  
Chronic Hemodialysis ◽  
Current Evidence ◽  
Icu Outcome ◽  
Stage Renal Disease ◽  
End Stage

Patients with end-stage renal disease (ESRD) experience higher rates of hospitalisation, cardiovascular events, and all-cause mortality and are more likely to require admission to the intensive care unit (ICU) than patients with normal renal function. Sepsis and cardiovascular diseases are the most common reasons for ICU admission. ICU mortality rates in patients requiring chronic hemodialysis are significantly higher than for patients without ESRD; however, dialysis patients have a better ICU outcome than those with acute kidney injury (AKI) requiring renal replacement therapy suggesting that factors other than loss of renal function contribute to their prognosis. Current evidence suggests, the longer-term outcomes after discharge from ICU may be favourable and that long-term dependence on dialysis should not prejudice against prompt referral or admission to ICU.

scholarly journals Assessment of decrease in renal function associated with hypothyroidism

2021 ◽  
Vol 12 (1) ◽  
pp. 275-286
Author(s):  
Ayesha Ammar ◽  
Kahkashan Bashir Mir ◽  
Sadaf Batool ◽  
Noreen Marwat ◽  
Maryam Saeed ◽  
...  
Keyword(s):  
Renal Function ◽  
Confidence Interval ◽  
Creatinine Clearance ◽  
Confidence Intervals ◽  
Standard Error ◽  
Radioactive Iodine ◽  
T Test ◽  
Euthyroid State ◽  
Significant Difference ◽  
The Mean

Objective: Study was aimed to see the effects of hypothyroidism on GFR as a renal function. Material and methods: Total of Fifty-eight patients were included in the study. Out of those forty-eight patients were female and the rest were male. Out of fifty eight patients, fifty three patients were of thyroid cancer in which hypothyroidism was due to discontinuation of thyroxine before the administration of radioactive iodine for Differentiated thyroid cancer.Moreover, remaining five patients were post radioactive iodine treatment (for hyperthyroidism) hypothyroid. All of the patients were above eighteen years of age with TSH value > 30µIU/ml. Pregnant and lactating females were excluded.Renal function tests (urea/creatinine, creatinine clearance) and serum electrolytes followed by Tc-99m-DTPA renal scan for GFR assessment (GATES’ method) were carried out in all subjects twice during the study, One study during hypothyroid state (TSH > 30 µIU/ml) and other during euthyroid state (TSH between 0.4 to 4µ IU/ml). The results of Student’s t-test showed significant difference in renal functions (Urea, creatinine, creatinine clearance, GFR values) in euthyroid state and hypothyroid state (p-value <0.05). RESULTS: In case of creatinine the paired t test reveal the mean 1.014±0.428, with standard error of 0.669 within 95% confidence interval, for creatinine clearance 80.11±14.12 with standard error of 1.94 within 95% confidence intervals, for urea the mean 28±12.13 with standard error of 1.607 within 95% confidence intervals and for GFR for individual kidney is 38.056±8.56 with standard error of 1.3717 within 95% confidence interval. There was no difference in the outcome of the 2 groups. Conclusion: Hypothyroidism impairs renal function to a significant level and hence needs to be prevented and corrected as early as possible.

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