Investigating Clinically Adequate Concentrations of Oseltamivir Carboxylate in End-Stage Renal Disease Patients Undergoing Hemodialysis Using a Population Pharmacokinetic Approach

Kamal, Mohamed; Lien, Kayla Yi Ting; Robson, Richard; Subramoney, Vishak; Clinch, Barry; Rayner, Craig R.; Gibiansky, Leonid

doi:10.1128/aac.01024-15

Cited by 5 publications

(2 citation statements)

References 22 publications

(32 reference statements)

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“…The dose of oseltamivir used for treatment and prophylaxis in our center was directed by the recommended dose for patients with ESRD receiving HD 15 . Although the ideal regimen for treating influenza in these patients is uncertain, pharmacokinetics studies showed that a 30 mg dose of oseltamivir given after HD sessions, provides sufficient exposure to allow safe and effective anti-influenza treatment and prophylaxis 16,17 .…”

Section: Discussionmentioning

confidence: 99%

Influenza A (H1N1): outbreak management in a dialysis unit and clinical outcomes of infection in chronic hemodialysis patients

et al. 2020

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Introduction: Chronic hemodialysis (HD) patients are considered to be at high risk for infection. Here, we describe the clinical outcomes of chronic HD patients with influenza A (H1N1) infection and the strategies adopted to control an outbreak of influenza A in a dialysis unit. Methods: Among a total of 62 chronic HD patients, H1N1 infection was identified in 12 (19.4%). Of the 32 staff members, four (12.5%) were found to be infected with the H1N1 virus. Outcomes included symptoms at presentation, comorbidities, occurrence of hypoxemia, hospital admission, and clinical evaluation. Infection was confirmed by real-time reverse transcriptase polymerase chain reaction. Results: The 12 patients who had H1N1 infection did not differ significantly from the other 50 non-infected patients with respect to age, sex, dialysis vintage, dialysis modality, or proportion of comorbidities. Obesity was higher in the H1N1-infected group (41.5 vs. 4%, p<0.002). The most common symptoms were fever (92%), cough (92%), and rhinorrhea (83%). Early empirical antiviral treatment with oseltamivir was started in symptomatic patients and infection control measures, including the intensification of contact-reduction measures by the staff members, antiviral chemoprophylaxis to asymptomatic patients undergoing HD in the same shift of infected patients, and dismiss of staff members suspected of being infected, were implemented to control the spread of infection in the dialysis unit. Conclusion: The clinical course of infection with H1N1 in our patients was favorable. None of the patients developed severe disease and the strategies adopted to control the outbreak were successful.

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Section: Discussionmentioning

confidence: 99%

Influenza A (H1N1): outbreak management in a dialysis unit and clinical outcomes of infection in chronic hemodialysis patients

et al. 2020

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“…Numerous oseltamivir population PK models have been developed to evaluate PK for specific purposes including impact of obesity, pregnancy, end‐stage renal dysfunction, ontogeny in infants younger than 1 year and the impact of probenecid to incite a drug–drug interaction . Whilst fit for their specific purpose, such models were too narrow for application in this program.…”

Section: Discussionmentioning

confidence: 99%

Interdisciplinary pharmacometrics linking oseltamivir pharmacology, influenza epidemiology and health economics to inform antiviral use in pandemics

Kamal

Smith

Chaiyakunapruk

et al. 2017

Brit J Clinical Pharma

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A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios. METHODSThe pharmacology module consisted of a pharmacokinetic distribution of oseltamivir carboxylate daily area under the concentration-time curve at steady state (simulated for 75 mg and 150 mg twice daily regimens for 5 days) and a pharmacodynamic distribution of viral shedding duration obtained from phase II influenza inoculation data. The epidemiological module comprised a susceptible, exposed, infected, recovered (SEIR) model to which drug effect on the basic reproductive number (R 0 ), a measure of transmissibility, was linked by reduction of viral shedding duration. The number of infected patients per population of 100 000 susceptible individuals was simulated for a series of pandemic scenarios, varying oseltamivir dose, R 0 (1.9 vs. 2.7), and drug uptake (25%, 50%, and 80%). The number of infected patients for each scenario was entered into the health economics module, a decision analytic model populated with branch probabilities, disease utility, costs of hospitalized patients developing complications, and case-fatality rates. Change in quality-adjusted life years was determined relative to base case. British Journal of Clinical Pharmacology RESULTSOseltamivir 75 mg relative to no treatment reduced the median number of infected patients, increased change in quality-adjusted life years by deaths averted, and was cost-saving under all scenarios; 150 mg relative to 75 mg was not cost effective in low transmissibility scenarios but was cost saving in high transmissibility scenarios. CONCLUSIONThis methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• To date, modelling of influenza has been conducted in discrete discipline areas.• The discrete pharmacology, epidemiology and health economic models are not linked and make assumptions about the adjacent disciplines that are inappropriate.• There are no epidemiological or health economic models which have taken into account between subject variability in the pharmacology of influenza treatments. WHAT THIS STUDY ADDS• This study provides the first integrated interdisciplinary framework to understand the cost-utility of antiviral therapy under various influenza pandemic scenarios linking drug pharmacokinetics/pharmacodynamics, epidemiological and health economics endpoints. • This quantitative framework was able to show that oseltamivir reduced the median number of infected individuals, increased quality-adjusted life years by deaths averted, and was cost-saving under most pandemic scenarios.• Given the growing need to justify pricing of medicines to society and payer, the methodology of interdisciplinary pharmacometrics can be applied across all disease areas where the pharmacokinetics/pharmacodynamics, clinical or epidemi...

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Evaluation of Hemodialysis Effect on Pharmacokinetics of Meropenem/Vaborbactam in End‐Stage Renal Disease Patients Using Modeling and Simulation

Zhuang

Wei

et al. 2020

The Journal of Clinical Pharma

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The objectives of this study were to evaluate the effect of hemodialysis (HD) on the pharmacokinetics (PK) of meropenem/vaborbactam, an approved beta‐lactam/beta‐lactamase inhibitor combination, and provide the rationale for the recommended timing of meropenem/vaborbactam administration relative to HD in end‐stage renal disease (ESRD) patients. Population PK models were developed separately for meropenem and vaborbactam in subjects with normal renal function and different degrees of renal impairment, including those receiving HD. Simulations were performed to evaluate the exposure of meropenem and vaborbactam in ESRD patients who received a fixed dose of 0.5 g/0.5 g meropenem/vaborbactam every 12 hours as a 3‐hour intravenous infusion under various drug administration schedules relative to HD. The probability of target attainment (PTA) analyses were conducted with pharmacokinetic/pharmacodynamic (PK/PD) targets of meropenem and vaborbactam. Simulations showed that HD reduces the accumulation of vaborbactam, but the exposure of vaborbactam is still above the PK/PD target regardless of whether meropenem/vaborbactam is administered predialysis or postdialysis. For meropenem, drug infusion completed right prior to initiation of HD may substantially reduce exposure leading to poor PTA results. In contrast, drug infusion completed at least 2 hours prior to initiation of HD is not predicted to result in efficacy loss based on PTA analysis. The results of simulation indicate that meropenem/vaborbactam infusion completed at least 2 hours prior to initiation of HD or administered immediately after the end of HD can avoid potential efficacy loss in ESRD patients.

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Investigating Clinically Adequate Concentrations of Oseltamivir Carboxylate in End-Stage Renal Disease Patients Undergoing Hemodialysis Using a Population Pharmacokinetic Approach

Cited by 5 publications

References 22 publications

Influenza A (H1N1): outbreak management in a dialysis unit and clinical outcomes of infection in chronic hemodialysis patients

Influenza A (H1N1): outbreak management in a dialysis unit and clinical outcomes of infection in chronic hemodialysis patients

Interdisciplinary pharmacometrics linking oseltamivir pharmacology, influenza epidemiology and health economics to inform antiviral use in pandemics

Evaluation of Hemodialysis Effect on Pharmacokinetics of Meropenem/Vaborbactam in End‐Stage Renal Disease Patients Using Modeling and Simulation

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