Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy

Smetana, Keaton S.; Cook, Aaron M.; Bastin, Melissa L. Thompson; Oyler, Douglas R.

doi:10.1016/j.jcrc.2016.06.023

Cited by 28 publications

(25 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…12 Therefore, CRRT could be a preferred option in critically ill patients with neurological injuries. 12,13 Patients who undergo CRRT may potentially experience refractory seizures from underexposure of therapy, whereas serious adverse effects may appear in those who are overexposed. To date, limited clinical studies assessing the impact of CRRT on AEDs have been reported and no standardized dosing recommendations have been established.…”

Section: How Might This Change Clinical Pharmacol-ogy or Translationamentioning

confidence: 99%

“…To date, limited clinical studies assessing the impact of CRRT on AEDs have been reported and no standardized dosing recommendations have been established. 13 Levetiracetam (LEV) is a commonly used anti-epileptic medication in the ICU with US Food and Drug Administration (FDA) approved indications for partial onset seizures, myoclonic seizures, and primary generalized tonic-clonic seizures in pediatric and adult patients. 14,15 Currently, guidelines also suggest that LEV can be used off-label for seizure prophylaxis in patients with severe traumatic brain injury or subarachnoid hemorrhage for no more than 7 days.…”

Section: How Might This Change Clinical Pharmacol-ogy or Translationamentioning

confidence: 99%

See 1 more Smart Citation

A Practice‐Based, Clinical Pharmacokinetic Study to Inform Levetiracetam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration (PADRE‐01)

Kalaria

Armahizer

McCarthy

et al. 2020

Clinical Translational Sci

View full text Add to dashboard Cite

Limited data exist on the effect of continuous renal replacement therapy (CRRT) methods on anti‐epileptic drug pharmacokinetics (PK). This prospective practice‐based PK study aims to assess the impact of continuous venovenous hemofiltration (CVVH), a modality of CRRT, on levetiracetam PK in critically ill patients and to derive individualized dosing recommendations. Eleven patients receiving oral or intravenous levetiracetam and CVVH in various intensive care units at a large academic medical center were enrolled to investigate the need for dosing adjustments. Prefilter, postfilter, and ultrafiltrate samples were obtained before dosing, after the completion of the infusion or 1‐hour postoral dose, and up to 6 additional time points postinfusion or postoral administration. Patient‐specific blood and ultrafiltrate flow rates and laboratory values were also collected at the time of sampling. The average sieving coefficient (SC) for levetiracetam was 0.89 ± 0.1, indicating high filter efficiency. Six of the 11 patients experienced concentrations outside the reported therapeutic range (12–46 mg/L). The average volume of distribution was 0.73 L/kg. CVVH clearance contributes a major fraction of the total levetiracetam clearance (36–73%) in neurocritically ill patients. The average bias and precision of the estimated vs. observed total clearance value was ~ 10.6% and 21.5%. Major dose determinants were identified to be SC and effluent flow rate. Patients with higher ultrafiltrate rates will have increased drug clearance and, therefore, will require higher doses in order to match exposures seen in patients with normal renal function.

show abstract

Section: How Might This Change Clinical Pharmacol-ogy or Translationamentioning

confidence: 99%

Section: How Might This Change Clinical Pharmacol-ogy or Translationamentioning

confidence: 99%

A Practice‐Based, Clinical Pharmacokinetic Study to Inform Levetiracetam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration (PADRE‐01)

Kalaria

Armahizer

McCarthy

et al. 2020

Clinical Translational Sci

View full text Add to dashboard Cite

show abstract

“…Because of the difficulty of predicting free VPA serum concentration and the inaccuracy of albumin-based normalizing formula for total serum concentration, researchers have advocated for more direct monitoring of free VPA serum concentration [7,10,11]. Although various therapeutic ranges of free VPA serum concentration, such as 5-15 or 7-23 mcg/mL, have been proposed in the literature, the optimal range remains undetermined [14,15]. This study investigated the relationship between free VPA serum concentration and adverse effects to determine the optimal clinical safety range.…”

Section: Introductionmentioning

confidence: 99%

Safety range of free valproic acid serum concentration in adult patients

et al. 2020

View full text Add to dashboard Cite

Background Therapeutic drug monitoring (TDM) is recommended during valproic acid (VPA) use, and total serum concentration has been widely adopted. However, the free form of VPA is responsible for its pharmacologic and toxic effects, and the total and free concentrations are highly discordant because of VPA's highly protein bound and saturable binding characteristics. Therefore, free VPA monitoring is increasingly advocated. Nevertheless, the correlation between free VPA concentration and associated adverse effects remains unknown. Objective To determine the optimal safety range of free VPA concentration in adult patients. Materials and methods This prospective cohort study enrolled adult patients undergoing VPA therapy with TDM. Patient characteristics, VPA use, and adverse effects (thrombocytopenia, hyperammonemia, and hepatotoxicity) were recorded. A multivariate logistic regression model was applied to identify the predictors of adverse effects, and the receiver operating characteristic curve was applied to locate the cutoff point of free VPA concentration. Results A total of 98 free serum concentrations from 51 patients were included for final analysis. In total, 31 (31.6%), 27 (27.6%), and 4 (4.1%) episodes of hyperammonemia, thrombocytopenia, and hepatotoxicity were observed, respectively. Free VPA concentration was a predicting factor for thrombocytopenia but not for hyperammonemia. A free VPA concentration of >14.67 mcg/mL had the greatest discriminating power (area under the curve = 0.77) for the occurrence of thrombocytopenia.

show abstract

“…Moreover, although plasma concentrations of LTG have been associated with efficacy in the prevention of epileptic seizures, the therapeutic ranges of LTG vary between individuals, especially enzymes and isoenzymes that affect plasma LTG levels [2][3][4][5][6][7][8][9][10][11][12]. Renal replacement therapy also influenced plasma concentrations of LTG [13][14]. Therefore, LTG should be quantitatively detected in the blood of patients to avoid drug toxicity caused by individual differences and environmental and pathological changes in the process of drug taking.…”

Section: Introductionmentioning

confidence: 99%

Development of a Simple Lc Method for Quantification of Lamotrigine in Human Serum

Mennickent¹,

Albornoz²,

Diego³

et al. 2020

J. Chil. Chem. Soc.

View full text Add to dashboard Cite

A liquid chromatographic (LC) method for quantitative analysis of lamotrigine in human serum was developed using liquid-liquid extraction with ethyl acetate. Quantitation was achieved over the concentration range of 1.0 to 40.0 µg/mL (r = 0.999), using a mixture of acetonitrile: phosphate buffer (0.5 M) of pH 4.5 (69:31 v/v) as mobile phase, with a flow of 1 mL min − 1. Column was C18 (150 mm x 4.6 mm, 5 cm; Merck), chloramphenicol was used as internal standard, and UV detection at α 306 nm. The intra-assay variation was between 1.22 % and 1.85 % and the inter-assay was between 1.72 % and 2.91 %. The detection limit was 0.14 µg/mL, and the quantification limit was 0.42 µg/mL. The method proved to be accurate, with a recovery between 94.02 % and 109.95 %, with RSD not higher than 2.91 % and was selective for lamotrigine (Rs between lamotrigine and chloramphenicol was 4.9). This method was successfully applied to quantify lamotrigine in patient serum samples. In conclusion, the method is precise, accurate, reproducible and selective for the analysis of lamotrigine in human serum. Therefore, it could be an important tool to evaluate drug level in this matrix and, of this way, to obtain a better drug effect.

show abstract

Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy

Cited by 28 publications

References 75 publications

A Practice‐Based, Clinical Pharmacokinetic Study to Inform Levetiracetam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration (PADRE‐01)

A Practice‐Based, Clinical Pharmacokinetic Study to Inform Levetiracetam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration (PADRE‐01)

Safety range of free valproic acid serum concentration in adult patients

Development of a Simple Lc Method for Quantification of Lamotrigine in Human Serum

Contact Info

Product

Resources

About