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.

scholarly journals Pharmacokinetics of Rosiglitazone in Patients with End-Stage Renal Disease

2002 ◽  
Vol 30 (4) ◽  
pp. 391-399 ◽  
Author(s):  
K Thompson-Culkin ◽  
B Zussman ◽  
AK Miller ◽  
MI Freed
Keyword(s):  
End Stage Renal Disease ◽  
Healthy Individuals ◽  
Time Curve ◽  
End Stage Renal Failure ◽  
Concentration Time ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage

The pharmacokinetics and tolerability of a single 8-mg oral dose of rosiglitazone, an anti-diabetic agent, were compared in 10 long-term haemodialysis patients and 10 healthy volunteers. Haemodialysis patients received rosiglitazone 4 h after haemodialysis (non-dialysis day) and 3 h before haemodialysis (dialysis day). Haemodialysis did not influence rosiglitazone pharmacokinetics, and dialytic clearance was low (0.10 l/h). The mean area under the concentration-time curve (AUC(0–∞)), the maximum observed plasma concentration ( Cmax) and the half-life for rosiglitazone were similar in haemodialysis patients (non-dialysis day) and healthy individuals (2192 ± 598 ng.h/ml versus 2388 ± 494 ng.h/ml, 338 ± 114 ng/ml versus 373 ± 95 ng/ml, and 3.70 ± 0.75 h versus 3.81 ± 0.86 h, respectively). AUC(0−∞) and Cmax were not markedly influenced by haemodialysis. Rosiglitazone dose adjustments are not warranted in patients with type 2 diabetes with end-stage renal failure on haemodialysis.

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.)

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 Neutrophil to Lymphocyte Ratio in Patients with End Stage Renal Disease in Benue State University Teaching Hospital, Makurdi, Nigeria

2020 ◽  
Vol 3 (1) ◽  
pp. 250-255
Author(s):  
MO Ogiator ◽  
JE Ojobi ◽  
OO Ijachi
Keyword(s):  
Renal Disease ◽  
Systemic Inflammation ◽  
Teaching Hospital ◽  
End Stage Renal Disease ◽  
Healthy Subjects ◽  
University Teaching ◽  
State University ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage

Chronic Kidney Disease (CKD) leads to end-stage renal disease (ESRD) and cardiovascular events. An important determinant of progression in CKD is chronic systemic inflammation which can be evaluated using the neutrophil to lymphocyte ratio (NLR). We aimed to investigate the value of NLR in patients with ESRD compared with healthy subjects. This was a retrospective study that analyzed data from patients with end-stage renal disease and equal number of age and sex matched control (healthy subjects) seen at Benue State University Teaching Hospital Makurdi from October 1st, 2012 to 31st December 2015. Out of the 118 patients studied 70(59.3) were males while 48 (40.7) were females. The mean age of the study population was 45.9 ± 16.4. The mean NLR for patients with ESRD was 3.55± 4.01 while that of healthy subjects was 1.29± 0.25. The mean NLR for patients was 3.47±4.01 for males and 3.68±4.06 for females while for the healthy subjects the mean NLR was 1.30±0.27 for males 1.27±0.22 for females. This study revealed elevated NLR in patients with ESRD. NLR reflects systemic inflammation. The availability of this ratio (NLR) can help improve outcome of patients with CKD.

The pharmacokinetics of oxycodone and its metabolites following single oral doses of Remoxy®, an abuse-deterrent formulation of extended-release oxycodone, in patients with hepatic or renal impairment

2015 ◽  
Vol 11 (2) ◽  
pp. 157 ◽  
Author(s):  
Bimal K. Malhotra, PhD ◽  
Grant L. Schoenhard, PhD ◽  
Annelies W. De Kater, PhD ◽  
Nadav Friedmann, PhD, MD
Keyword(s):  
Renal Function ◽  
Hepatic Impairment ◽  
Impaired Renal Function ◽  
Extended Release ◽  
Phase 1 ◽  
Hepatic Function ◽  
Maximum Plasma ◽  
Time Curve ◽  
Impaired Hepatic Function ◽  
Oral Doses

Objective: Remoxy® (Pain Therapeutics, Inc., Austin, TX) is an abuse-deterrent formulation of extended-release oxycodone. The effects of renal or hepatic impairment on the pharmacokinetics (PK) of single, oral doses of Remoxy 20 or 10 mg, respectively, were assessed in two phase 1 studies in subjects aged 18-80 years.Methods: PK parameters included maximum plasma concentration (Cmax) and area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t), and extrapolated to infinity (AUCinf). Adverse events (AEs) were monitored.Results: Mean (SD) oxycodone Cmax values following Remoxy 20-mg administration were 17.6 (9.1), 21.9 (11.2), 25.9 (18.2), and 31.6 (14.5) ng/mL and AUC0-t values were 210.7 (82.1), 271.6 (83.3), 299.5 (76.3), and 493.5 (175.9) ng·h/mL in subjects with normal or mild (n = 6 each), moderate (n = 5), and severely impaired renal function (n = 6), respectively. Mean (SD) oxycodone Cmax following Remoxy 10-mg administration was 7.6 (3.3), 7.8 (2.3), and 13.1 (5.3) ng/mL and AUC0-t was 105.7 (49.5), 134.7 (38.3), and 218.0 (74.1) ng·h/mL in subjects with normal, mild, and moderately impaired hepatic function (n = 6 each), respectively. Differences in exposure values between the different renal and hepatic groups were significant. Treatment-emergent AEs were reported by 14.3, 66.7, 66.7, and 50.0 percent of subjects with normal, mild, moderate, and severely impaired renal function, respectively, and by 50.0, 33.3, and 66.7 percent of subjects with normal, mild, and moderately impaired hepatic function, respectively.Conclusions: As renal or hepatic function decreased, oxycodone Cmax and AUC0-t were up to approximately twofold higher following single, oral doses of extended-release Remoxy. AEs were those typically reported for opioids. Lower doses of Remoxy may thus be safely prescribed to subjects with renal or hepatic impairment.

scholarly journals Neutrophil to Lymphocyte Ratio in Patients with End Stage Renal Disease in Benue State University Teaching Hospital, Makurdi, Nigeria

2020 ◽  
Vol 3 (1) ◽  
pp. 250-255
Author(s):  
MO Ogiator ◽  
JE Ojobi ◽  
OO Ijachi
Keyword(s):  
Renal Disease ◽  
Systemic Inflammation ◽  
Teaching Hospital ◽  
End Stage Renal Disease ◽  
Healthy Subjects ◽  
University Teaching ◽  
State University ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage

Chronic Kidney Disease (CKD) leads to end-stage renal disease (ESRD) and cardiovascular events. An important determinant of progression in CKD is chronic systemic inflammation which can be evaluated using the neutrophil to lymphocyte ratio (NLR). We aimed to investigate the value of NLR in patients with ESRD compared with healthy subjects. This was a retrospective study that analyzed data from patients with end-stage renal disease and equal number of age and sex matched control (healthy subjects) seen at Benue State University Teaching Hospital Makurdi from October 1st, 2012 to 31st December 2015. Out of the 118 patients studied 70(59.3) were males while 48 (40.7) were females. The mean age of the study population was 45.9 ± 16.4. The mean NLR for patients with ESRD was 3.55± 4.01 while that of healthy subjects was 1.29± 0.25. The mean NLR for patients was 3.47±4.01 for males and 3.68±4.06 for females while for the healthy subjects the mean NLR was 1.30±0.27 for males 1.27±0.22 for females. This study revealed elevated NLR in patients with ESRD. NLR reflects systemic inflammation. The availability of this ratio (NLR) can help improve outcome of patients with CKD.

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