Dataset Information

Lidocaine as treatment for neonatal seizures: Evaluation of previously developed population pharmacokinetic models and dosing regimen.

ABSTRACT:

Aims

Lidocaine is used to treat neonatal seizures refractory to other anticonvulsants. It is effective, but also associated with cardiac toxicity. Previous studies have reported on the pharmacokinetics of lidocaine in preterm and term neonates and proposed a dosing regimen for effective and safe lidocaine use. The objective of this study was to evaluate the previously developed pharmacokinetic models and dosing regimen. As a secondary objective, lidocaine effectiveness and safety were assessed.

Methods

Data from preterm neonates and (near-)term neonates with and without therapeutic hypothermia receiving lidocaine were included. Pharmacokinetic analyses were performed using non-linear mixed effects modelling. Simulations were performed to evaluate the proposed dosing regimen. Lidocaine was considered effective if no additional anticonvulsant was required and safe if no cardiac adverse events occurred.

Results

Data were available for 159 neonates; 50 (31.4%) preterm and 109 term neonates, of whom 49 (30.8%) were treated with therapeutic hypothermia. Lidocaine clearance increased with postmenstrual age by 0.69%/day (95% confidence interval 0.54-0.84%). During therapeutic hypothermia (33.5°C), lidocaine clearance was reduced by 21.8% (7.26%/°C, 95% confidence interval 1.63-11.2%) compared to normothermia (36.5°C). Simulations demonstrated that the proposed dosing regimen leads to adequate average lidocaine plasma concentrations. Effectiveness and safety were assessed in 92 neonates. Overall effectiveness was 53.3% (49/92) and 56.5% (13/23) for neonates receiving the proposed dosing regimen. No cardiac toxicity was observed.

Conclusion

Lidocaine pharmacokinetics was adequately described across the entire neonatal age range. With the proposed dosing regimen, lidocaine can provide effective and safe treatment for neonatal seizures.

SUBMITTER: Favie LMA

PROVIDER: S-EPMC6983510 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Lidocaine as treatment for neonatal seizures: Evaluation of previously developed population pharmacokinetic models and dosing regimen.

Favié Laurent M A LMA Huitema Alwin D R ADR van den Broek Marcel P H MPH Rademaker Carin M A CMA de Haan Timo R TR van Straaten Henrica L M HLM Simons Sinno H P SHP Rijken Monique M Nuytemans Debbie H G M DHGM Egberts Toine C G TCG Groenendaal Floris F

British journal of clinical pharmacology 20200103 1

<h4>Aims</h4>Lidocaine is used to treat neonatal seizures refractory to other anticonvulsants. It is effective, but also associated with cardiac toxicity. Previous studies have reported on the pharmacokinetics of lidocaine in preterm and term neonates and proposed a dosing regimen for effective and safe lidocaine use. The objective of this study was to evaluate the previously developed pharmacokinetic models and dosing regimen. As a secondary objective, lidocaine effectiveness and safety were as ...[more]

PMID: 31663153

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Project description:Objectives: Teicoplanin has been extensively used in the treatment for infections caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). However, current teicoplanin treatment is challenging due to relatively low and variable concentrations under standard dosage regimens. This study aimed to investigate the population pharmacokinetics (PPK) characteristics of teicoplanin in adult sepsis patients and provide recommendations for optimal teicoplanin dosing regimens. Methods: A total of 249 serum concentration samples from 59 septic patients were prospectively collected in the intensive care unit (ICU). Teicoplanin concentrations were detected, and patients' clinical data were recorded. PPK analysis was performed using a non-linear, mixed-effect modeling approach. Monte Carlo simulations were performed to evaluate currently recommended dosing and other dosage regimens. The optimal dosing regimens were defined and compared by different pharmacokinetic/pharmacodynamic parameters, including trough concentration (Cmin), the ratio of 24-h area under the concentration-time curve to the minimum inhibitory concentration (AUC0-24/MIC), as well as the probability of target attainment (PTA) and the cumulative fraction of response (CFR) against MRSA. Results: A two-compartment model adequately described the data. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance and peripheral compartment volume were 1.03 L/h, 20.1 L, 3.12 L/h and 101 L, respectively. Glomerular filtration rate (GFR) was the only covariate that significantly affected teicoplanin clearance. Model-based simulations revealed that 3 or 5 loading doses of 12/15 mg/kg every 12 h followed by a maintenance dose of 12/15 mg/kg every 24 h-72 h for patients with different renal functions were required to achieve a target Cmin of 15 mg/L and a target AUC0-24/MIC of 610. For MRSA infections, PTAs and CFRs were not satisfactory for simulated regimens. Prolonging the dosing interval may be easier to achieve the target AUC0-24/MIC than reducing the unit dose for renal insufficient patients. Conclusion: A PPK model for teicoplanin in adult septic patients was successfully developed. Model-based simulations revealed that current standard doses may result in undertherapeutic Cmin and AUC, and a single dose of at least 12 mg/kg may be needed. AUC0-24/MIC should be preferred as the PK/PD indicator of teicoplanin, if AUC estimation is unavailable, in addition to routine detection of teicoplanin Cmin on Day 4, follow-up therapeutic drug monitoring at steady-state is recommended.

Dataset Information

Lidocaine as treatment for neonatal seizures: Evaluation of previously developed population pharmacokinetic models and dosing regimen.

Aims

Methods

Results

Conclusion

Publications

Lidocaine as treatment for neonatal seizures: Evaluation of previously developed population pharmacokinetic models and dosing regimen.

Similar Datasets

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