Clinical Pharmacokinetics in Kidney Disease

Lea‐Henry, Tom; Carland, Jane E.; Stocker, Sophie L.; Sevastos, Jacob; Roberts, Darren M.

doi:10.2215/cjn.00340118

Cited by 153 publications

(144 citation statements)

References 47 publications

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“…However, knowledge of a drug's pharmacology, place in therapy, and pharmacokinetic and pharmacodynamic consideration can aid the clinician in optimizing antibiotic use to maximize efficacy and minimize adverse effects in patients. Resources and guidelines do exist to aid in dose optimization (61)(62)(63), although the recommendations are not consistent or applicable in all clinical situations (e.g., AKI, different modalities of kidney replacement therapies) (4,64). A list of resources for dosing medications in patients with CKD has been included in Supplemental Table 1.…”

Section: Sulfamethoxazole-trimethoprimmentioning

confidence: 99%

“…In a United States Medicare cohort of patients newly started on hemodialysis between 1996 and 2001, the 12-month incidence of infection-related hospitalization was 32% (1,2). Antibiotic optimization in CKD and ESKD can often be quite complicated, as these patients may have altered pharmacokinetics (absorption, distribution, metabolism, and elimination) and are often at increased risk of side effects (3,4). Dialysis comes with additional considerations as well, as there are periods of increased clearance during dialysis followed by 48-72 hours of relatively little antibiotic clearance between dialysis sessions.…”

Section: Introductionmentioning

confidence: 99%

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Clinical Pharmacology of Antibiotics

Eyler

Shvets

2019

CJASN

114

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Antimicrobial pharmacology and its effect on prescribing is quite complex. Selecting an antibiotic that will optimally treat an infection while minimizing adverse effects and the development of resistance is only the first step, as one must also consider the patient's individual pharmacokinetic alterations and the pharmacodynamic properties of the drug when prescribing it as well. Patients with CKD may have alterations in their protein binding, volumes of distribution, kidney clearance, and nonrenal clearance that necessitates antibiotic dose adjustments to prevent the development of toxicity. Knowledge of a drug's pharmacodynamics, defined as the relationship between drug exposure and antibacterial efficacy, provides some guidance regarding the optimal way to make dose adjustments. Different pharmacodynamic goals, such as maximizing the time that free (unbound) drug concentrations spend above the minimum inhibitory concentration (MIC) for time dependent drugs (e.g., b-lactams) or maximizing the free peak-to-MIC ratio for concentration-dependent antibiotics (e.g., aminoglycosides), require different adjustment strategies; for instance, decreasing the dose while maintaining normal dosing frequency or giving normal (or even larger) doses less frequently, respectively. Patients receiving hemodialysis have other important prescribing considerations as well. The nephrologist or patient may prefer to receive antibiotics that can be administered intravenously toward the end of a dialysis session. Additionally, newer dialysis technologies and filters can increase drug removal more than originally reported. This review will discuss the place in therapy, mechanism of action, pharmacokinetic, pharmacodynamic, and other pharmacologic considerations encountered when prescribing commonly used antibiotics in patients with chronic kidney disease or ESKD.

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Section: Sulfamethoxazole-trimethoprimmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical Pharmacology of Antibiotics

Eyler

Shvets

2019

CJASN

114

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“…The important principles to consider include the therapeutic target, the initial dose, the maintenance dose, the dose frequency, and when a dosage adjustment should be performed. The key changes in pharmacokinetics that occur in a patient with kidney disease have been discussed elsewhere (2).…”

Section: General Principlesmentioning

confidence: 99%

“…Drugs are commonly prescribed in the management of patients with both chronic and acute kidney disease, and this population may have an increased risk of adverse drug reactions (1). Kidney diseases cause a range of changes to pharmacokinetics, as discussed in part 1 of this series (2), so these must be considered when designing appropriate dosage regimens.…”

Section: Introductionmentioning

confidence: 99%

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Clinical Pharmacokinetics in Kidney Disease

Roberts

Sevastos

Carland

et al. 2018

CJASN

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A change in pharmacokinetics can alter drug exposure and predispose the patient to either over-or underdosing, potentially resulting in adverse drug reactions or therapeutic failure. Kidney disease is characterized by multiple physiologic effects, which induce clinically significant changes in pharmacokinetics. These vary between individuals and may be quantitated in certain instances. An understanding of pharmacokinetic concepts is, therefore, important for a rational approach to the design of drug dosing regimens for the delivery of personalized medical care. Whether kidney disease is acute or chronic, drug clearance decreases and the volume of distribution may remain unchanged or increase. AKI is defined by dynamic changes in kidney function, which complicates attempts to accurately quantify drug clearance. In contrast, changes in drug clearance progress more slowly with CKD. In general, kidney replacement therapies increase drug clearance, but the extent to which this occurs depends on the modality used and its duration, the drug's properties, and the timing of drug administration. However, the changes in drug handling associated with kidney disease are not isolated to reduced kidney clearance and an appreciation of the scale of potential derangements is important. In most instances, the first dose administered in patients with kidney disease is the same as in patients with normal kidney function. However, in some cases, a higher (loading) initial dose is given to rapidly achieve therapeutic concentrations, followed by a lower maintenance dose, as is well described when prescribing anti-infectives to patients with sepsis and AKI. This review provides an overview of how pharmacokinetic principles can be applied to patients with kidney disease to personalize dosage regimens. Patients with kidney disease are a vulnerable population and the increasing prevalence of kidney disease means that these considerations are important for all prescribers.

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Prescription and Dispensation of QT-Prolonging Medications in Individuals Receiving Hemodialysis

Wang,

Assimon

et al. 2024

JAMA Netw Open

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ImportanceIndividuals with dialysis-dependent kidney failure have numerous risk factors for medication-related adverse events, including receipt of care by multiple clinicians and initiation of some QT-prolonging medications with known risk of torsades de pointes (TdP), which is associated with higher risk of sudden cardiac death. Little is known about the prescription and dispensation patterns of QT-prolonging medications among people receiving dialysis, hindering efforts to reduce drug-related harm from these and other medications in this high-risk population.ObjectiveTo examine prescription and dispensation patterns of QT-prolonging medications with known TdP risk and selected interacting medications prescribed to individuals receiving hemodialysis.Design, Setting, and ParticipantsThis cross-sectional study included patients 60 years or older who were enrolled in Medicare Parts A, B, and D receiving in-center hemodialysis from January 1 to December 31, 2019. Analyses were conducted from October 20, 2022, to June 16, 2023.ExposuresNew-user prescriptions for the 7 most frequently filled QT-prolonging medications characterized by the timing of the new prescription relative to acute care encounters, the type of prescribing clinician and pharmacy that dispensed the medication, and concomitant use of selected medications known to interact with the 7 most frequently filled QT-prolonging medications with known TdP risk.Main Outcomes and MeasuresThe main outcomes were the frequencies of the most commonly filled and new-use episodes of QT-prolonging medications; the timing of medication fills relative to acute care events; prescribers and dispensing pharmacy characteristics for new use of medications; and the frequency and types of new-use episodes with concurrent use of potentially interacting medications.ResultsOf 20 761 individuals receiving hemodialysis in 2019 (mean [SD] age, 74 [7] years; 51.1% male), 10 992 (52.9%) filled a study drug prescription. Approximately 80% (from 78.6% for odansetron to 93.9% for escitalopram) of study drug new-use prescriptions occurred outside of an acute care event. Between 36.8% and 61.0% of individual prescriptions originated from general medicine clinicians. Between 16.4% and 26.2% of these prescriptions occurred with the use of another QT-prolonging medication. Most potentially interacting drugs were prescribed by different clinicians (46.3%-65.5%).Conclusions and RelevanceIn this cross-sectional study, QT-prolonging medications for individuals with dialysis-dependent kidney failure were commonly prescribed by nonnephrology clinicians and from nonacute settings. Prescriptions for potentially interacting medications often originated from different prescribers. Strategies aimed at minimizing high-risk medication-prescribing practices in the population undergoing dialysis are needed.

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Clinical Pharmacokinetics in Kidney Disease

Cited by 153 publications

References 47 publications

Clinical Pharmacology of Antibiotics

Clinical Pharmacology of Antibiotics

Clinical Pharmacokinetics in Kidney Disease

Prescription and Dispensation of QT-Prolonging Medications in Individuals Receiving Hemodialysis

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