Population Pharmacokinetics and Dosing Recommendations of Levetiracetam in Adult and Elderly Patients With Epilepsy

Hernández-Mitre, María Patricia; Medellín‐Garibay, Susanna Edith; Rodríguez‐Leyva, Ildefonso; Rodríguez-Pinal, Cristian Jazmín; Zarazúa, Sergio; Jung‐Cook, Helgi; Roberts, Jason A.; Romano‐Moreno, Silvia; Milán‐Segovia, Rosa del Carmen

doi:10.1016/j.xphs.2020.02.018

Cited by 15 publications

(22 citation statements)

References 40 publications

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“…Eight of the fourteen studies enrolled paediatric patients [15, 17, 18, 20, 21, 24-26]; 2 studies were conducted in neonates [18, 21], 4 studies in children less than 18 years of age [15, 20, 25, 26], and 2 studies included both children and adults [17, 24]. Three study only enrolled adults [13, 14, 19], and the other three studies included elderly patients of over 70 years [16, 22, 23].…”

Section: Resultsmentioning

confidence: 99%

“…The LEV PK for oral formulations was described with a one-compartment model with first-order absorption and elimination, and for injections was described with a one- or two- compartment model with first order elimination. Two studies conducted in neonates [18, 21], three in children [20, 26], and five in adults were based on sparse sampling data from the routine clinical TDM settings [16, 17, 19, 22, 23], and other four studies included intensive sampling data [13-15, 25]. The number of participants in each study ranged from 7 to 524, with LEV observations per individual ranging from 1 to 10.…”

Section: Resultsmentioning

confidence: 99%

“…The characteristics of each study are summarised in Table 1. Sneck et al [13] enrolled only healthy subjects, Pigeolet et al included both patients and healthy subjects [14], and the other studies were conducted in patients with epilepsy [15][16][17][18][19][20][21][22][23][24][25][26]. Eight of the fourteen studies enrolled paediatric patients [15,17,18,20,21,[24][25][26]; 2 studies were conducted in neonates [18,21], 4 studies in children less than 18 years of age [15,20,25,26], and 2 studies included both children and adults [17,24].…”

Section: Study Characteristicsmentioning

confidence: 99%

“…perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted August 6, 2020. ; https://doi.org/10.1101/2020.08.05.20167239 doi: medRxiv preprint study only enrolled adults [13,14,19], and the other three studies included elderly patients of over years [16,22,23].…”

Section: Study Characteristicsmentioning

confidence: 99%

“…For children, Toublanc et al (2008) [25] recommended that the dosage should be differentiated as per body weight: 10 mg/kg for children less than 20 kg; 250 mg twice daily for children between 20 and 40 kg, and 500 mg twice daily for children more than 40 kg. For adults, Herná ndez-Mitre et al [16] recommended to adjust the dosage according to eGFR to achieve the trough LEV concentrations between 12 and 46 μg/mL. All rights reserved.…”

Section: Comparison Of Studiesmentioning

confidence: 99%

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A Review of Population Pharmacokinetic Studies of Levetiracetam

Wang

Zhu

et al. 2020

Preprint

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Background: Levetiracetam has been widely used as a treatment option for different types of epilepsy in both adults and children. Because of its large between-subject variability, several population pharmacokinetic studies have been performed to identify its pharmacokinetic covariates, and thus facilitate individualised therapy. Objective: The aim of this review was to provide a synopsis for population pharmacokinetic studies of levetiracetam and explore identified influencing covariates. Methods: We systematically searched PubMed and Embase databases from inception to June 30, 2020. The information on study designs, target population, model characteristics, and identified covariates were summarised. Moreover, the pharmacokinetic profiles were compared among neonates, children, and adults. Results: A total of 14 studies were included, among which two involved neonates, four involved children, two involved both children and adults, and six involved only adults. The median value of apparent clearance for children (0.074 [range: 0.038 to 0.079] L/h/kg) was higher than that for adults (0.054 [range: 0.039 to 0.061] L/h/kg). Body weight was found to influence the apparent clearance and volume of distribution significantly, whereas renal function influenced the clearance. Likewise, co-administration with enzyme-inducing antiepileptic drugs (such as carbamazepine and phenytoin) increased the drug clearance by 9 to 22%, whereas coadministration with valproate acid decreased it by 18.8%. Conclusion: Levetiracetam dose regimen is dependent on the body size and renal function of patients. Further studies are needed to evaluate levetiracetam pharmacokinetics in neonates and pregnant women.

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