Pharmacokinetics and renal excretion of desmopressin after intravenous administration to healthy subjects and renally impaired patients

Agersø, Henrik; Larsen, Lotte Seiding; Riis, A.; Lövgren, Ulf; Karlsson, Mats O.; Senderovitz, Thomas

doi:10.1111/j.1365-2125.2004.02175.x

Cited by 69 publications

(44 citation statements)

References 30 publications

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“…Nonlinear mixed effects modeling was used and a 1-compartmental model with first order absorption was able to describe the data well. In previous studies, more complex models such as a 2-compartmental model [35], a 3-compartmental model [36] and a 1-compartmental model with transit compartments [15] have been used to describe DDAVP PK. The first two, however, describe DDAVP pharmacokinetics after intravenous dosing, which indeed follow biphasic kinetics [37].…”

Section: Discussionmentioning

confidence: 99%

Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children

et al. 2016

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Introduction: Desmopressin is used for nocturnal enuresis treatment in children. In this study, we investigated the pharmacokinetics of two formulations: a tablet and a lyophilisate, in both fasted and fed children.Methods: Previously published data from two studies (22 children aged 6 to 16 yr and 25 children aged 6 to 13 yr) were analyzed using population pharmacokinetic modeling. A 1-compartment model with first order absorption was fitted to the data. Covariates were selected using a forward selection procedure. The final model was evaluated, and sensitivity analysis was performed to improve future sampling designs. Simulations were subsequently performed to further explore the relative bioavailability of both formulations and the food effect.Results: The final model described the desmopressin plasma concentrations adequately.Formulation and fed state were included as covariates on the relative bioavailability. The lyophilisate was on average 32.1 % more available than the tablet, and fasted children exhibited an average increase in relative bioavailability of 101%, compared to fed children. Body weight was included as a covariate on distribution volume, using a power function with exponent 0.402.Simulations suggest both the formulation and the food effect are clinically relevant. Conclusions:Bioequivalence data of two formulations of the same drug in adults, cannot be readily extrapolated to children. This is the first study in children suggesting that the two desmopressin formulations in children are not bioequivalent at the currently approved dose levels.Furthermore, the effect of food intake was found to be clinically relevant. Sampling times for a future study were suggested. This sampling design should result in more informative data and consequently generate a more robust model. Key points Population pharmacokinetic modeling was applied to pediatric desmopressin PK data and used to extract more information out of existing pediatric drug data, generate new information and improve the collection of future information. In this study it was found that the established bioequivalence of desmopressin in adults might be different in the pediatric population. A profound food effect was also quantified. In order to make solid conclusions regarding desmopressin efficacy in children, PK and PD data should be gathered simultaneously in a well-designed study, for which some design suggestions are presented in this paper. Abbreviations

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Section: Discussionmentioning

confidence: 99%

Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children

et al. 2016

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“…[ 47 ] One of the strategies employed for stabilizing peptide derivatives is replacing L -amino acids with D -amino acids. [47][48][49] Therefore, we have designed our NDI series using nonnatural D -phenylalanine derivatives. We have also carried out cellular toxicity tests on both L -and D -NDI series to compare and assess the effect of the amino acid confi guration on cellular viability (for details vide infra and Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Thermally Reduced Graphene Oxide Nanohybrids of Chiral Functional Naphthalenediimides for Prostate Cancer Cells Bioimaging

Tyson

Mirabello

Calatayud

et al. 2016

Adv Funct Materials

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This study reports on the supramolecular assemblies formed between planar carbon systems (PCSs) such as thermally reduced graphene oxide (TRGO) and its small‐molecule model system coronene and a series of d‐ and l‐α amino acid derivatized naphthalenediimides (NDIs) where the halogen substituents (X = F, Cl, Br, I) are varied systematically. Confocal fluorescence microscopy of NDIs, NDI•coronene, and NDI•TRGO complexes is performed proving the uptake and stability of such complexes in the cellular environment and suggesting their potential as prostate cancer imaging agents. 1H NMR and UV–vis spectroscopy studies support the formation of charge transfer complexes whereby the increasing polarizability and general electronegativity of the aryl halide substituted at the NDI periphery influence the magnitude of the association constants in the ground state between NDI and coronene. Complexation between NDIs and PCSs also results in stable photoexcited assemblies within the solution (coronene) as well as the dispersed phased (TRGO). Fluorescence emission titrations and 2‐photon time correlated single photon counting measurements suggest the existence of dynamic quenching mechanisms upon the excitation of the fluorophore in the presence of the carbon substrates, as these methods are sensitive proves for the subtle changes in the NDI environment. The series of halogenated species used exerts supramolecular control over the degree of surface assembly on the TRGO and over the interactions with the coronene molecule, and this is of relevance to the assembly of future biosensing platforms as these materials can both be viewed as congeners of graphene. Finally, MTT assays carried out in PC‐3 cells demonstrate that the stable noncovalent functionalization of TRGO and coronene with either l or d NDIs remarkably improves the cellular viability in the presence of such graphene‐like materials. These phenomena are of particular relevance for the understanding of the direct donor–acceptor interactions in solutions which govern the design of nanomaterials with future biosensing and bioimaging applications.

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“…Hence, it will be necessary to consider other detection strategies to increase the possibility to detect the misuse of this peptide.by LC-MS. According to Agerso et al [20], an important fraction of desmopressin is eliminated from the body via renal clearance.…”

Section: Methods Applicationmentioning

confidence: 99%

“…These methods provided sensitive and cost effective analyses [8,[18][19][20][21][22], but with some important limitations, in particular concerning specificity [23].…”

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confidence: 99%

Qualitative detection of desmopressin in plasma by liquid chromatography–tandem mass spectrometry

et al. 2012

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This work describes a liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) method for detection of desmopressin in human plasma in the low femtomolar range.Desmopressin is a synthetic analogue of the antidiuretic hormone arginine vasopressin and it might be used by athletes as masking agent in the frame of blood passport controls. Therefore, it was recently added by the World Anti-Doping Agency (WADA) to the list of prohibited substances in sport as a masking agent. Mass spectrometry characterization of desmopressin was performed with a high-resolutionOrbitrap-based mass spectrometer. Detection of the peptide in the biological matrix was achieved using a triple quadrupole instrument with an electrospray ionization (ESI) interface after protein precipitation, weak cation solid phase extraction and HPLC separation with an octadecyl reverse phase column. Identification of desmopressin was performed using three product ions, m/z 328.0, m/z 120.0, and m/z 214.0, from the parent ion, m/z 535.5.The extraction efficiency of the method at the limit of detection was estimated at 40% (n=10), the ion suppression at 5% (n=10), and the limit of detection was 50 pg/ml (S/N> 3).Selectivity of the method was verified against several endogenous and synthetic desmopressin related peptides. The performance and the applicability of the method were tested by analysis of clinical samples after administration of desmopressin via intravenous, oral, and intranasal routes. Only after intravenous administration, desmopressin could be successfully detected.3

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Pharmacokinetics and renal excretion of desmopressin after intravenous administration to healthy subjects and renally impaired patients

Cited by 69 publications

References 30 publications

Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children

Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children

Thermally Reduced Graphene Oxide Nanohybrids of Chiral Functional Naphthalenediimides for Prostate Cancer Cells Bioimaging

Qualitative detection of desmopressin in plasma by liquid chromatography–tandem mass spectrometry

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