Noha N Salama

Publications (23) View all

• Article: Daptomycin pharmacokinetics and pharmacodynamics in a pooled sample of patients receiving thrice-weekly hemodialysis.

  Jill M Butterfield, Bruce A Mueller, Nimish Patel, Katie E Cardone, Darren W Grabe, Noha N Salama, Thomas P Lodise
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  ABSTRACT: While the pharmacokinetic (PK) properties of daptomycin in hemodialysis (HD) patients have been evaluated previously by three groups, resultant dosing recommendations have varied. To address this clinical conundrum, this study combined concentration-time data from these PK evaluations and derived uniform dosing recommendations among patients on HD receiving daptomycin. A two compartment model with separate HD and non-HD clearance terms was fit to the PK data from these studies with BigNPAG. Embedded with PK parameters from the population PK analysis, 5,000-subject Monte Carlo simulations (MCS) were performed to identify HD dosing schemes which provide efficacy (cumulative and daily area-under-the-curve [lsqb]AUC[rsqb] values) and toxicity (trough concentrations ≥ 24.3 mg/liter) profiles comparable to simulations employing the daptomycin PK model derived from the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) study. Separate HD dosing schemes were sought for the two weekly interdialytic periods (48 and 72 hours). For the 48 hour interdialytic period, intra- and post-HD dosing provided the most isometric cumulative and daily AUCs. For the 72 hour interdialytic period, all HD dosing schemes provided AUC(48-72) values < 50% of SAB-IE AUC(48-72) values. Increasing the parent dose by 50% intra- or post-HD provided comparable AUC(48-72) while maintaining acceptable C(min) values. When efficacy and toxicity profiles were evaluated for each individual study, higher probabilities of C(min) ≥ 24.3 mg/liter were observed in one of the three studies. Given the high probability of C(min) ≥ 24.3 mg/liter in one of the three studies, more intensive creatine phosphokinase (CPK) monitoring may be warranted in HD patients receiving daptomycin.
  Antimicrobial Agents and Chemotherapy 12/2012; · 4.84 Impact Factor
• Article: Longitudinal hemodiafilter performance in modeled continuous renal replacement therapy.

  Deborah A Pasko, Mariann D Churchwell, Noha N Salama, Bruce A Mueller
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  ABSTRACT: With advanced anticoagulation, many institutions operate continuous renal replacement therapy (CRRT) circuits longer than manufacturers' recommendations. This extended use may change hemodiafilter performance and clearance properties. However, hemodiafilter performance over time has not been assessed. We investigated solute clearance over time in modeled CRRT. In vitro continuous hemofiltration (CH) and continuous hemodialysis (CD) were operated for 48 h using AN69 polyacrylonitrile, cellulose triacetate, F70 polysulfone, and Optiflux F160NR polysulfone hemodiafilters with citrated bovine blood. Urea, creatinine, gentamicin, vancomycin, and albumin clearances were assessed in CH (ultrafiltration rates = 1 and 3 l/h). Clearances of urea, creatinine, gentamicin, and albumin, were assessed in CD with dialysate flow rate of 2 l/h. Solute CH clearances were significantly higher at 3 l/h. Only creatinine and gentamicin clearances were affected by time. Creatinine CD clearance significantly declined at 48 h for all hemodiafilters, especially polysulfone hemodiafilters. CRRT duration affects solute transmembrane clearance. Clinicians should consider hemodiafilter age when assessing hemodialysis dose or drug clearance.
  Blood Purification 03/2011; 32(2):82-8. · 2.10 Impact Factor
• Article: Single-dose daptomycin pharmacokinetics in chronic haemodialysis patients.

  Noha N Salama, Jonathan H Segal, Mariann D Churchwell, Jignesh H Patel, Lihong Gao, Michael Heung, Bruce A Mueller
  Nephrology Dialysis Transplantation 11/2010; 25(11):3803. · 3.40 Impact Factor
• Article: Daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis.

  A Mary Vilay, Maricor Grio, Daryl D Depestel, Kevin M Sowinski, Lihong Gao, Michael Heung, Noha N Salama, Bruce A Mueller
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  ABSTRACT: To investigate daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis to develop dosing recommendations. Prospective, open-label pharmacokinetic study. : Intensive care units located within a teaching medical center. Eight adults with known/suspected Gram-positive infections receiving continuous venovenous hemodialysis and daptomycin. Daptomycin at 8 mg/kg intravenously over 30 mins. Serial blood and effluent samples were collected over the next 48 hrs. Daptomycin protein binding was determined by equilibrium dialysis. Daptomycin continuous venovenous hemodialysis transmembrane clearance was determined by dividing daptomycin effluent by serum concentrations and multiplying by mean effluent production rate for each subject. Equations describing a two-compartment, open-pharmacokinetic model were fitted to each subject's daptomycin concentration-time data and pharmacokinetic parameters were determined by standard methods. Serum concentration-time profiles were simulated for two daptomycin regimens (8 mg/kg every 48 hrs and 4 mg/kg every 24 hrs). A total of 7.7 ± 0.6 mg/kg (mean ± sd) of daptomycin was administered, resulting in an observed peak concentration of 81.2 ± 19.0 μg/mL. Daptomycin steady-state volume of distribution (0.23 ± 0.14 L/kg) and free fraction (17.5% ± 5.0%) were increased in critically ill subjects receiving continuous venovenous hemodialysis compared with previous values reported in healthy volunteers. Daptomycin transmembrane clearance (6.3 ± 2.9 mL/min) accounted for more than half of total clearance (11.3 ± 4.7 mL/min). Simulations demonstrated 8 mg/kg daptomycin every 48 hrs would result in higher peak (88.8 ± 20.0 μg/mL vs. 53.0 ± 12.3 μg/mL) and lower trough concentrations (7.2 ± 5.2 μg/mL vs. 12.3 ± 5.1 μg/mL) than 4 mg/kg every 24 hrs. Daptomycin at 8 mg/kg every 48 hrs in critically ill patients receiving continuous venovenous hemodialysis resulted in good drug exposure, achieved high peak concentrations to maximize daptomycin's concentration-dependent activity, and resulted in trough concentration that would minimize the risk of myopathy. CLINICALTRIALS.GOV IDENTIFIER: NCT00663403.
  Critical care medicine 09/2010; 39(1):19-25. · 6.37 Impact Factor
• Article: Etanercept clearance during an in vitro model of continuous venovenous hemofiltration.

  Geoffrey M Fleming, Noha N Salama, Saada K Eid, Kenneth R Cooke, Bruce A Mueller
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  ABSTRACT: Etanercept is a tumor necrosis factor-alpha antagonist used in inflammation-mediated conditions. Continuous venovenous hemofiltration (CVVH) has also been used in patients with inflammatory conditions. This study evaluated etanercept clearance using an in vitro CVVH model. Etanercept clearance was assessed in vitro in bovine blood at 1-3 mg/l final serum concentration, and urea control at 750 mg/l. CVVH was performed using polyacrylonitrile, polysulfone, and polymethylmethacrylate filters at 3 l/h ultrafiltrate and 200 ml/min blood flow rates. Transmembrane clearance was estimated using sieving coefficient calculations, and adsorptive removal rate was approximated using a mass balance calculation. Urea sieving coefficient remained constant (1.04 +/- 0.01). Ultrafiltrate etanercept concentrations were undetectable (sieving coefficient < 0.02) and transmembrane and adsorptive clearances were negligible. Etanercept is not cleared appreciably by transmembrane or adsorptive mechanisms in CVVH using polyacrylonitrile, polysulfone, or polymethylmethacrylate hemofilters.
  Blood Purification 09/2009; 28(4):348-53. · 2.10 Impact Factor