Tailored Assays for Pharmacokinetic and Pharmacodynamic Investigations of Aliskiren and Enalapril in Children: An Application in Serum, Urine, and Saliva

Burckhardt, Bjoern B.; Tins, Jutta; Ramusovic, Sergej; Läer, Stephanie

doi:10.5863/1551-6776-20.6.431

Cited by 5 publications

(6 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Primarily, immunoassays are preferable than LC-MS/MS. The importance of immunoassays is ascribed to their intrinsic advantages [ 17 ]. Chemiluminescence immunoassays (CLIAs) generally have many advantages over the other non-isotopic ELISA such as the high sensitivity and the wide dynamic range.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Development of a highly sensitive chemiluminescence immunoassay using a novel signal-enhanced detection system for quantitation of durvalumab, an immune-checkpoint inhibitor monoclonal antibody used for immunotherapy of lung cancer

Darwish

Alzoman

Khalil

et al. 2023

Heliyon

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

RETRACTED: Development of a highly sensitive chemiluminescence immunoassay using a novel signal-enhanced detection system for quantitation of durvalumab, an immune-checkpoint inhibitor monoclonal antibody used for immunotherapy of lung cancer

Darwish

Alzoman

Khalil

et al. 2023

Heliyon

View full text Add to dashboard Cite

“…Enalapril and enalaprilat were obtained as European Pharmacopeia Reference Standard. Study samples measured below the LLOQ were not included in the population pharmacokinetic modeling analysis (21).…”

Section: Methodsmentioning

confidence: 99%

Simultaneous Semi-Mechanistic Population Pharmacokinetic Modeling Analysis of Enalapril and Enalaprilat Serum and Urine Concentrations From Child Appropriate Orodispersible Minitablets

et al. 2019

Self Cite

View full text Add to dashboard Cite

Enalapril is recommended as the first line of therapy and is proven to improve survival rates for treatment of Pediatric Heart Failure; however, an approved drug and child appropriate dosage formulation is still absent. The present analysis was conducted to perform a detailed model informed population pharmacokinetic analysis of prodrug enalapril and its active metabolite enalaprilat in serum and urine. Further, a model informed dosage form population-pharmacokinetic analysis was conducted to evaluate differences in pharmacokinetics of enalapril and its active metabolite enalaprilat when prodrug was administered to 24 healthy adults in a crossover, two periods, two treatments, phase I clinical trial using child-appropriate orodispersible mini-tablets (ODMT) and reference (Renitec®) dosage formulation. A simultaneous semi-mechanistic population-pharmacokinetic model was developed using NONMEM software, which predicted full profile serum and urine concentrations of enalapril and enalaprilat. First-order conditional estimation with interaction was used for parameter estimation. Transit compartments added using Erlang distribution method to predicted enalapril absorption and enalaprilat formation phases. Normalized body weight was identified as covariate related to enalapril volume of distribution. Visual predictive check (VPC) plots and conducted bootstrap analysis validated the model. The data from the two formulations were pooled for population-pharmacokinetic analysis and covariate effect of the formulation was found on mean transit time (MTT1) of enalapril absorption. In addition, data of each formulation were modeled separately and the estimated parameters of each individual administered both formulations were correlated using paired samples Wilcoxon rank test ( p < 0.05 = significant) which also showed only a significant difference ( p = 0.03) in MTT1 i.e., 5 min early appearance of enalapril from ODMT compared to reference tablets. No difference in the pharmacokinetics of active enalaprilat was found from the ODMT compared to the reference formulation. The population pharmacokinetic analysis provided detailed information about the pharmacokinetics of enalapril and enalaprilat, which showed that the ODMT formulation might have similar pharmacodynamic response compared to the reference formulation.

show abstract

“…For determination of the PK of enalapril and enalaprilat, liquid chromatography-triple quadrupole tandem mass spectrometry followed by solid-phase extraction of serum samples was applied (Shimadzu HPLC 10 [Shimadzu, Duisburg, Germany] coupled with AB Sciex API 2000 mass spectrometer [Sciex, Darmstadt, Germany]) [27,38]. The ion transitions were mass-to-charge ratio (m/z) 377.2 to 234.2 m/z for enalapril, 349.1 to 206.1 m/z for enalaprilat, and 425.3 m/z to 351.2 m/z for the internal standard benazepril.…”

Section: Determination Of Enalapril and Enalaprilatmentioning

confidence: 99%

“…Study patients were treated with the newly developed enalapril ODMTs based on an age-appropriate dosing regimen developed by physiologically based modelling and simulation. Patients were systematically assessed for PK, PD [26][27][28] clinical parameters and ODMT acceptability and palatability [8]. This manuscript describes the primary and secondary objective concerning the pharmacokinetic study's endpoints, in which pediatric PK data of enalapril and enalaprilat were obtained in these children to characterize the rate and extent of the exposure in the pediatric population with DCM or CHD.…”

Section: Introductionmentioning

confidence: 99%

Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies)

et al. 2022

Self Cite

View full text Add to dashboard Cite

Angiotensin-converting enzyme inhibitors (ACEI), such as enalapril, are a cornerstone of treatment for pediatric heart failure which is still used off-label. Using a novel age-appropriate formulation of enalapril orodispersible minitablets (ODMTs), phase II/III open-label, multicenter pharmacokinetic (PK) bridging studies were performed in pediatric patients with heart failure due to dilated cardiomyopathy (DCM) and congenital heart disease (CHD) in five participating European countries. Children were treated for 8 weeks with ODMTs according to an age-appropriate dosing schedule. The primary objective was to describe PK parameters (area under the curve (AUC), maximal concentration (Cmax), time to reach maximal concentration (t-max)) of enalapril and its active metabolite enalaprilat. Of 102 patients, 89 patients (n = 26, DCM; n = 63 CHD) were included in the primary PK endpoint analysis. Rate and extent of enalapril and its active metabolite enalaprilat were described and etiology and age could be identified as potential PK modifying factors. The dosing schedule appeared to be tolerated well and did not result in any significant drug-related serious adverse events. The PK analysis and the lack of severe safety events supports the applied age-appropriate dosing schedule for the enalapril ODMTs.

show abstract

Tailored Assays for Pharmacokinetic and Pharmacodynamic Investigations of Aliskiren and Enalapril in Children: An Application in Serum, Urine, and Saliva

Cited by 5 publications

References 41 publications

RETRACTED: Development of a highly sensitive chemiluminescence immunoassay using a novel signal-enhanced detection system for quantitation of durvalumab, an immune-checkpoint inhibitor monoclonal antibody used for immunotherapy of lung cancer

RETRACTED: Development of a highly sensitive chemiluminescence immunoassay using a novel signal-enhanced detection system for quantitation of durvalumab, an immune-checkpoint inhibitor monoclonal antibody used for immunotherapy of lung cancer

Simultaneous Semi-Mechanistic Population Pharmacokinetic Modeling Analysis of Enalapril and Enalaprilat Serum and Urine Concentrations From Child Appropriate Orodispersible Minitablets

Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies)

Contact Info

Product

Resources

About