scholarly journals Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antoine G. Schneider ◽  
Pascal André ◽  
Joerg Scheier ◽  
Monika Schmidt ◽  
Heiko Ziervogel ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Total Body Clearance ◽  
Dosage Adjustment ◽  
Liposomal Amphotericin B ◽  
Beta Lactams ◽  
Significant Extent ◽  
Clinically Significant ◽  
Total Body ◽  
Body Clearance

AbstractCytokine hemoadsorption might be beneficial in patients with sepsis. However, its effect on anti-infective agents' disposition remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham extracorporeal circuit (controls) and to drug combinations (3 cases and 3 controls for each combination). Hemoadsorption was performed with CytoSorb (CytoSorbents Corporation, USA). We evaluated 17 drugs (clindamycin, fluconazole, linezolid, meropenem, piperacillin, anidulafungin, ganciclovir, clarithromycin, posaconazole, teicoplanin, tobramycin, ceftriaxone, ciprofloxacin, metronidazole, liposomal amphotericin B, flucloxacillin and cefepime). Repeated blood sampling from the extracorporeal circulation (adsorber inlet/outlet, sham circuit) was performed over six hours following administration. Total clearance and adsorber-specific clearance were computed. Hemoadsorption was associated with increased clearance of all study drugs, except ganciclovir. Its impact on total body clearance was considered as moderate for fluconazole (282%) and linezolid (115%), mild for liposomal amphotericin B (75%), posaconazole (32%) and teicoplanine (31%) and negligible for all other drugs. Hemoadsorber clearance declined over time, with even delayed desorption for beta-lactams. It was moderately correlated with drug's lipophilicity (p = 0.01; r2 = 0.43). Hemoadsorption with CytoSorb appears to increase to a clinically significant extent the clearance of five among 17 tested anti-infectives. Studies in human patients are required to confirm the need for dosage adjustment of these agents.

scholarly journals Pharmacokinetics of Anti-Infective Agents During CytoSorb Hemoadsorption: An Experimental Study

2020 ◽  
Author(s):  
Antoine Schneider ◽  
Pascal André ◽  
Joerg Scheier ◽  
Monika Schmidt ◽  
Heiko Ziervogel ◽  
...  
Keyword(s):  
Experimental Study ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Total Body Clearance ◽  
Liposomal Amphotericin B ◽  
Beta Lactams ◽  
Limited Effect ◽  
Clearance Studies ◽  
Total Body ◽  
Body Clearance

Abstract Background: Cytokine hemoadsorption might be effective in patients with sepsis. However, its effect on anti-infective agents' pharmacokinetics remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. Methods: This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham procedure (controls) and to a drug combination (3 cases and 3 controls for each combination). Hemoadsorption was performed with CytoSorb® (CytoSorbents Corporation, USA). We evaluated 17 drugs (clindamycin, fluconazole, linezolid, meropenem, piperacillin, anidulafungin, ganciclovir, clarithromycin, posaconazole, teicoplanin, tobramycin, ceftriaxone, ciprofloxacin, metronidazole, liposomal amphotericin B, flucloxacillin and cefepime). Repeated blood sampling from the extracorporeal circulation (adsorber inlet/outlet, sham circulation) were performed within six hours of administration. Total clearance and adsorber-specific clearances were computed at each time point.Results: Hemoadsorption was associated with increased clearance of all study drugs, except for ganciclovir. Its impact on total body clearance was major for fluconazole (+282%), linezolid (+115%) and amphotericin B (+75%). It was minor for posaconazole (+32%), teicoplanin (+31%), anidulafungin (+23%), piperacillin (+19%), flucloxacillin (+16%), metronidazole (+16%) and ciprofloxacin (+15%) and insignificant (<10%) for all other drugs. Hemoadsorber clearance declined over time with even delayed desorption for beta-lactams. It was moderately correlated with drug's lipophilicity (p=0.01; r2=0.43). Conclusions: Hemoadsorption with CytoSorb® has limited effect on the pharmacokinetics of most tested anti-infective drugs but appears to increase fluconazole, linezolid and liposomal amphotericin B clearance. Studies in humans with sepsis are required to confirm these findings.

Disposition of Foscarnet during Peritoneal Dialysis

1996 ◽  
Vol 30 (10) ◽  
pp. 1106-1109 ◽  
Author(s):  
Alicia CM Alexander ◽  
Adam Akers ◽  
Gary R. Matzke ◽  
Francesca T. Aweeka ◽  
Donald S. Fraley
Keyword(s):  
Renal Function ◽  
Peritoneal Dialysis ◽  
Serum Concentration ◽  
Normal Renal Function ◽  
Half Life ◽  
Total Body Clearance ◽  
Case Summary ◽  
Clinically Significant ◽  
Total Body ◽  
Body Clearance

OBJECTIVE: To report the disposition of foscarnet in a patient undergoing peritoneal dialysis. CASE SUMMARY: A 34-year-old man with AIDS received foscarnet for the treatment of esophageal cytomegalovirus. We characterized the clearance of foscarnet in this patient during continuous cyclic peritoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis (CAPD). DISCUSSION: The foscarnet half-lives during CCPD and CAPD were 41.4 and 45.8 hours, respectively. These values are significantly greater than the half-life of 4.5 hours observed in patients with normal renal function and about half that reported in anuric patients undergoing hemodialysis during the interdialytic period. The CCPD and CAPD clearances of foscarnet were 5.8 and 4.5 mL/min, respectively; the CAPD clearances of creatinine and urea nitrogen were 4.1 and 6.0 mL/min, respectively. The patient's estimated total body clearance values of foscarnet during CCPD and CAPD were 9.8 and 8.8 mL/min, respectively. Thus, CCPD and CAPD augmented the patient's residual clearance of foscarnet by 145% and 105%, respectively. CONCLUSIONS: Since incremental increases in residual clearance of 30% or more generally will result in clinically significant changes in a drug's serum concentration, foscarnet dosage needs to be individualized for patients receiving peritoneal dialysis.

scholarly journals 2109. Liposomal Amphotericin B-associated Nephrotoxicity in Obese and Non-obese Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S714-S714
Author(s):  
Brandon Tritle ◽  
Logan Peterson ◽  
Jared Olson ◽  
Emily Benefield ◽  
Paloma F Cariello ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Ideal Body Weight ◽  
Total Body Weight ◽  
Liposomal Amphotericin B ◽  
Obese Patients ◽  
Daily Dose ◽  
Ideal Body ◽  
Total Body

Abstract Background Liposomal amphotericin B (L-amb) is an important antifungal agent which exhibits significant rates of dose-dependent nephrotoxicity. Animal studies demonstrate only small amounts of L-amb distribute into adipose tissue and obese animals show greater risk of nephrotoxicity with L-amb administration. This study aims to determine whether obese patients are at a higher risk of nephrotoxicity with weight-based doses of L-amb. Methods We performed a multi-center, retrospective cohort study of nephrotoxicity with L-amb in obese (BMI > 30) and non-obese adult patients at University of Utah Health and Intermountain Healthcare from January 1, 2014 through December 31, 2018. Our primary outcome was the rate of nephrotoxicity as determined by AKIN criteria. Patients receiving at least one dose of L-amb were identified for inclusion. Patients were excluded if they were already on a renal replacement at the time of L-amb initiation or they received L-amb prior to admission. Results We included 221 patients, 47 (21%) were obese and 174 (79%) were non-obese. Median total body weight was 109 kg in obese patients compared with 70 kg in non-obese patients. Dosage based on ideal body weight was higher in the obese group (median 6.9 mg/kg vs. 4.9 mg/kg). Obese patients were significantly more likely to experience acute kidney injury (AKI) than non-obese patients (55% vs. 37%, P = 0.03). Patients who experienced nephrotoxicity received a higher average daily dose than those who did not (365 mg vs. 333 mg, P = 0.03), had a higher median cumulative dose (3,130 mg vs. 1,700 mg, P < 0.001), and had a higher median total body weight (79.6 kg vs. 71.9 kg, P = 0.04.). Additionally, daily dose normalized to total body weight was not associated with AKI (median 4.7 mg/kg in patients with AKI vs. 4.8 mg/kg in patients without AKI, P = 0.86). However, daily dose normalized to ideal body weight was associated with AKI (median 5.5 mg/kg in patients with AKI vs. 4.9 mg/kg in patients without AKI, P = 0.02). Conclusion We identified a higher rate of nephrotoxicity among obese patients receiving L-amb compared with non-obese patients. These data suggest that dosing L-amb based on total body weight places obese patients at a higher risk of nephrotoxicity. This should be considered when assessing the risks and benefits of this dosing strategy in obese patients. Disclosures All authors: No reported disclosures.

Decrease in Theophylline Clearance after the Administration of Erythromycin to a Patient with Obstructive Lung Disease

1983 ◽  
Vol 17 (5) ◽  
pp. 370-372 ◽  
Author(s):  
J.A. Green ◽  
W.A. Clementi
Keyword(s):  
Time Course ◽  
Total Body Clearance ◽  
Elevated Serum ◽  
Chronic Obstructive ◽  
Serum Theophylline ◽  
Obstructive Pulmonary Disease ◽  
Theophylline Disposition ◽  
Clinically Significant ◽  
Total Body ◽  
Body Clearance

It has been demonstrated previously that erythromycin can inhibit the total body clearance of theophylline, resulting in elevated serum theophylline concentrations. The overall incidence of this interaction and the population at risk have not been elucidated fully. Recent investigations have suggested that such an interaction is doubtful and that patients in whom this occurrence was suspect developed alterations in theophylline disposition secondary to worsening pulmonary function, not from erythromycin therapy alone. This case report shows that the interaction between theophylline and erythromycin can be clinically significant, producing as much as a 50-percent reduction in the total body clearance of the bronchodilator. The magnitude and time course of this interaction in patients with congestive heart failure and chronic obstructive pulmonary disease may differ considerably from that reported in healthy volunteers.

scholarly journals Evaluation of Total Body Weight versus Adjusted Body Weight Liposomal Amphotericin B Dosing in Obese Patients

2021 ◽  
Author(s):  
Michelle H. Ting ◽  
Andrej Spec ◽  
Scott T. Micek ◽  
David J. Ritchie ◽  
Tamara Krekel
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Critically Ill ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Total Body Weight ◽  
Liposomal Amphotericin B ◽  
Obese Patients ◽  
Definitive Therapy ◽  
Total Body

Liposomal amphotericin B (LAmB) is used for various fungal infections, but it is unclear which dosing weight to use in obese patients. The purpose of this study was to compare clinical outcomes of adjusted body weight (adjBW) versus total body weight (TBW) dosing of LAmB. This single-center, retrospective cohort study included patients who received LAmB for definitive therapy, whose TBW exceeded 120% of their ideal body weight (IBW). Analyses were conducted for 3 mg/kg adjBW versus TBW, and 5 mg/kg adjBW versus TBW. A total of 238 patients were included. For the 68 patients who received LAmB 3 mg/kg, there were no differences in safety or efficacy outcomes. For the 170 patients who received LAmB 5 mg/kg, significantly more patients in the TBW group experienced the primary outcome of nephrotoxicity (57% vs. 35%, p-value 0.016), and had significantly higher rates of early discontinuation of LAmB due to toxicity (33% vs. 17%, p = 0.030). There was a trend towards increased 90-day mortality in the adjBW group (60% vs. 45%, p = 0.079); however, adjBW dosing was not associated with increased mortality in an adjusted model. Given lower rates of nephrotoxicity but a possible trend towards increased mortality, in patients whose TBW exceeds 120% of IBW, dosing LAmB by adjBW may be reasonable in patients who are not critically ill and who have lower risk infections. In critically ill patients or those with fungal pathogens or sites of infection associated with higher mortality risk, dosing by TBW can be considered.

Methods for particle size reduction of liposomal amphotericin B

2018 ◽  
Vol 60 (1) ◽  
pp. 42-45
Author(s):  
Tuan Quang Nguyen ◽  
Van Lam Nguyen ◽  
Thai Son Nguyen ◽  
Thi Minh Hue Pham ◽  
◽  
...  
Keyword(s):  
Particle Size ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Size Reduction ◽  
Liposomal Amphotericin B ◽  
Particle Size Reduction

scholarly journals Efficacy of Intravenous Liposomal Amphotericin B (AmBisome) against Coccidioidal Meningitis in Rabbits

2002 ◽  
Vol 46 (8) ◽  
pp. 2420-2426 ◽  
Author(s):  
Karl V. Clemons ◽  
Raymond A. Sobel ◽  
Paul L. Williams ◽  
Demosthenes Pappagianis ◽  
David A. Stevens
Keyword(s):  
Spinal Cord ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
White Blood Cells ◽  
Clinical Signs ◽  
Liposomal Amphotericin B ◽  
Coccidioides Immitis ◽  
Lower Protein ◽  
Motor Abnormalities ◽  
The Brain

ABSTRACT The efficacy of intravenously administered liposomal amphotericin B (AmBisome [AmBi]) for the treatment of experimental coccidioidal meningitis was compared with those of oral fluconazole (FLC) and intravenously administered conventional amphotericin B (AMB). Male New Zealand White rabbits were infected by intracisternal inoculation of arthroconidia of Coccidioides immitis. Starting 5 days postinfection, animals received one of the following: 5% dextrose water diluent; AMB given at 1 mg/kg of body weight; AmBi given at 7.5, 15, or 22.5 mg/kg intravenously three times per week for 3 weeks; or oral FLC given at 80 mg/kg for 19 days. One week after the cessation of therapy, all survivors were euthanatized, the numbers of CFU remaining in the spinal cord and brain were determined, and histological analyses were performed. All AmBi-, FLC-, or AMB-treated animals survived and had prolonged lengths of survival compared with those for the controls (P < 0.0001). Treated groups had significantly lower numbers of white blood cells and significantly lower protein concentrations in the cerebrospinal fluid compared with those for the controls (P < 0.01 to 0.0005) and had fewer clinical signs of infection (e.g., weight loss, elevated temperature, and neurological abnormalities including motor abnormalities). The mean histological scores for AmBi-treated rabbits were lower than those for FLC-treated and control rabbits (P < 0.016 and 0.0005, respectively); the scores for AMB-treated animals were lower than those for the controls (P < 0.0005) but were similar to those for FLC-treated rabbits. All regimens reduced the numbers of CFU in the brain and spinal cord compared with those for the controls (P ≤0.0005). AmBi-treated animals had 3- to 11-fold lower numbers of CFU than FLC-treated rabbits and 6- to 35-fold lower numbers of CFU than AmB-treated rabbits. Three of eight animals given 15 mg of AmBi per kg had no detectable infection in either tissue, whereas other doses of AmBi or FLC cleared either the brain or the spinal cord of infection in fewer rabbits. In addition, clearance of the infection from both tissues was achieved in none of the rabbits, and neither tissue was cleared of infection in AMB-treated animals. Overall, these data indicate that intravenously administered AmBi is superior to oral FLC or intravenous AMB and that FLC is better than AMB against experimental coccidioidal meningitis. These data indicate that AmBi may offer an improvement in the treatment of coccidioidal meningitis. Additional studies are warranted.

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