scholarly journals Evaluation of Two Fosphenytoin Loading Dose Regimens and Monitoring in Infants and Neonates Less Than Six Months of Age

2020 ◽  
Vol 25 (7) ◽  
pp. 617-622
Author(s):  
Kristin K. Bohannon ◽  
Noelle Leung ◽  
Aaron M. Cook ◽  
Elizabeth Autry ◽  
Julia Gibson ◽  
...  

OBJECTIVES The objectives of the study were to compare the free serum concentrations after different fosphenytoin loading dose strategies in patients younger than 6 months old and to investigate the frequency of seizure cessation following a loading dose of fosphenytoin. METHODS This retrospective cohort study included neonates and infants admitted to a 150-bed children's hospital between August 1, 2014, and February 1, 2018. Patients were included if they were younger than 6 months old and had a postload free phenytoin serum concentration collected during the specified time frame. Patients were identified through a database query screening for the inclusion criteria. Patients were separated into 2 groups with the 15 mg/kg group as per protocol and the 20 mg/kg group as noted in common practice. Data collection included demographic information, fosphenytoin dose, time of administration of the fosphenytoin loading dose, time of sampling, free phenytoin serum concentration results, concomitant antiepileptic agents, albumin serum concentration, and total bilirubin serum concentration. RESULTS Forty-one patients were included for analysis, 12 in the 15 mg/kg group and 29 in the 20 mg/kg group. The average free phenytoin concentration after the loading dose was 2.45 ± 0.54 mg/L in the 15 mg/kg group and 2.52 ± 0.66 mg/L in the 20 mg/kg group. Seizure cessation after the fosphenytoin loading dose was achieved in 3 of 12 (25%) patients in the 15 mg/kg group and in 13 of 29 (45%) patients in the 20 mg/kg group (p = 0.305). CONCLUSIONS The study demonstrates that a traditional range of fosphenytoin loading dose (15–20 mg/kg) led to elevated postloading dose free phenytoin serum concentrations in the majority of patients with a seizure cessation rate of approximately 39%. The question remains as to what the optimal dose and target concentration should be in this patient population to achieve the best efficacy without risking associated toxicities.

2019 ◽  
Vol 104 (7) ◽  
pp. e2.31-e2
Author(s):  
Ibrahim Vhora ◽  
Andrew Taylor

AimThe trust has implemented the use of therapeutic drug monitoring (TDM) of teicoplanin on intensive care following research that identified great variability in population pharmacokinetics in children.1–3 The summary of the research available showed that patients are not achieving target concentrations. This retrospective audit aimed to evaluate whether patients were achieving target serum concentrations. It also evaluated whether teicoplanin TDM was correctly completed for each patient. The following objectives were set based on grey literature and the Summary of Product Characteristics:4 Evaluate if serum concentrations are being taken on or after day 4 post initiation (steady state), and within 1 hour pre-dose (trough) Assess if serum concentrations reach target concentration with standard initial BNFC dosing appropriate for the indication of treatment.MethodsA retrospective report of teicoplanin serum concentrations was provided by the biochemistry labs covering a 6 month period. This report was used to identify the patients for the audit. For each patient: dose information, times and clinical particulars were obtained via the electronic prescribing system, Meditech version 6. If needed, clinical records were obtained from the medical records archive.Results71 serum concentrations were identified. 11 were excluded due to unobtainable or incomplete data. Serum concentrations were then evaluated for accuracy. The criteria set for determining accuracy were: Serum concentration taken on or after day 4 post initiation (steady state) Serum concentration taken within 1 hour pre dose (trough) Patient prescribed correct BNFC dosing regimen 55% (n=33) of patients had all 3 criteria met for an accurate concentration to be determined. This meant 45% of our patients serum concentrations could not be used to accurately evaluate if current dosing regimens promptly achieve target concentrations. Using the patients’ serum concentrations that followed the above criteria, it was found that 64% of these patients did not reach their desired target concentration. This included patients with: endocarditis (n=5) – aiming for trough greater than 30 mg/L cystic fibrosis (n=1) – aiming for trough greater than 20 mg/L other infections such as sepsis (n=27) – aiming for trough greater than 15 mg/L No patient included in this audit that required a higher target concentration reached their target before the first serum concentration.ConclusionIt is evident that teicoplanin TDM, which is still in its infancy at the trust, requires further support to improve practice. From the serum concentrations that were carried out correctly, this audit begins to illustrate a number of issues surrounding teicoplanin dosing in paediatric patients, especially those with difficult to treat infections. Further research is required to assess how these correlate to clinical outcome in practice as well as evaluating patients not in an intensive care setting. This study can be a driving force for a larger scale study to be carried out so that recommendations can be established and a change of practice can be implemented.ReferencesRamos-Martín V, Paulus S, Siner S, et al. Population Pharmacokinetics of Teicoplanin in Children. J Antimicrob. Chemother 2014;58: 6920–6927Harding I, Macgowan AP, White LO, et al. Teicoplanin therapy for Staphylococcus aureus septicaemia: relationship between pre-dose serum concentrations and outcome. J. Antimicrob. Chemother 2000;45:835–841.Reed MD, Yamashita TS, Myers CM, et al. The pharmacokinetics of teicoplanin in infants and children. J. Antimicrob. Chemother 1997;39:789–796.Targocid 400mg [Internet]. Targocid 400mg - Summary of Product Characteristics (SmPC) - (eMC). Available from: https://www.medicines.org.uk/emc/product/2927 (Accessed 20 February 2018)


1986 ◽  
Vol 20 (6) ◽  
pp. 481-484 ◽  
Author(s):  
Jamie T. Gilman ◽  
Peter Gal

The efficacy of the FDA guidelines for theophylline dosing in newborns was evaluated retrospectively in 224 patients who had clearance data available. Mean projected post loading dose serum concentration was 4.1 ± 1.0 mg/L in 160 patients. Mean projected steady-state concentration was 4.8 ± 1.6 mg/L in 189 patients receiving intravenous aminophylline and 4.2 ± 1.3 mg/L in 35 patients on oral therapy. Projected serum concentrations were subtherapeutic (<6.0 mg/L) in 181 of the 224 patients analyzed. There was a statistically significant difference in serum concentrations between asphyxiated and nonasphyxiated patients (p<0.001). There was no significant difference in mean projected serum concentrations between patients age 26–41 weeks (postconceptional age). This study suggests that the FDA dosing guidelines for theophylline in infants is inadequate and results in subtherapeutic (<6.0 mg/L) serum concentrations in the majority of newborns.


2019 ◽  
Vol 20 (4) ◽  
pp. 346-351 ◽  
Author(s):  
Nadielle S. Bidu ◽  
Bruno J.D. Fernandes ◽  
Eduardo J.C. Dias ◽  
Jucelino N.C. Filho ◽  
Regina E.A. Bastos ◽  
...  

Background: Vancomycin is used mostly to overcome infections caused by methicillinresistant microorganisms. There are no well-established administration protocols for neonates and infants, so the leak of a specific administration regime in that population may lead to serum concentrations beyond the specified range. Objective: This case series evaluated the pharmacokinetics adjustment from a vancomycin therapeutic regimen prescribed to neonates and infants with bacterial infection at a neonatal public hospital intensive- care-unit, with the primary purpose to verify cases of nephrotoxicity. Methods: Three neonates and four infants taking vancomycin therapy, hospitalized in a public hospital from November 2014 to March 2015, were included in the study. Vancomycin serum concentrations were determined by particle-enhanced-turbidimetric inhibition-immunoassay. The vancomycin concentrations were used for dose adjustment by USC*Pack-PC-Collection®, a non-parametric maximization program. The trough serum concentration range of 10 to 20mg.L-1 was considered therapeutic. Results: Three patients had serum concentration outside the reference-range, one with subtherapeutic, and two with supratherapeutic concentrations. All patients had concomitant use of drugs which interfered with vancomycin distribution and excretion pharmacokinetics parameters, including drugs that may enhance nephrotoxicity. One patient showed signs of acute renal damage, by low vancomycin and creatinine estimated clearances. Conclusion: The pharmacokinetic adjustment has been proven to be a useful and necessary tool to increase therapeutic efficacy and treatment benefits. The standard dose of vancomycin can be used to initiate therapy in neonates and infants admitted to the ICU, but after reaching the drug steady state, the dosing regimen should be individualized and guided by pharmacokinetic parameters.


2001 ◽  
Vol 94 (3) ◽  
pp. 385-389 ◽  
Author(s):  
Patrick K. Birmingham, AF1-0567 ◽  
Michael J. Tobin ◽  
Dennis M. Fisher ◽  
Thomas K. Henthorn ◽  
Steven C. Hall ◽  
...  

Background Recent studies have determined that an initial rectal acetaminophen dose of approximately 40 mg/kg is needed in children to achieve target antipyretic serum concentrations. The timing and amount of subsequent doses after a 40-mg/kg dose has not been clarified for this route of administration. Based on the authors' previous pharmacokinetic data, they examined whether a 40-mg/kg loading dose followed by 20-mg/kg doses at 6-h intervals maintain serum concentrations within the target range of 10-20 microg/ml, without evidence of accumulation. Methods Children (n = 16) received rectal acetaminophen (40 mg/kg) and up to three additional doses of 20 mg/kg at 6-h intervals. Venous blood samples were taken every 30 min for 4 h, then every 60 min for 4 h, and every 4 h for 16 h. The authors assessed whether their published pharmacokinetic parameters predicted the acetaminophen concentrations in the present study. They also assessed their dosing regimen by determining the fraction of time each individual maintained the target concentration. Results All patients received the initial loading dose; 10 of 16 patients received three subsequent doses. Serum concentrations with the initial dose were in the target range 38 +/- 25% of the time. With subsequent dosing, the target range was maintained 60 +/- 29% of the time. The highest serum concentration with initial or subsequent dosing was 38.6 microg/ml. Pharmacokinetic parameters from the earlier study predicted the serum concentrations observed for both initial and subsequent doses. Conclusions A rectal acetaminophen loading dose of 40 mg/kg followed by 20-mg/kg doses every 6 h results in serum concentrations centered at the target range of 10-20 microg/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.


2017 ◽  
Vol 7 (1) ◽  
pp. 13-15
Author(s):  
Amy VandenBerg ◽  
Jessica Broadway ◽  
Callie Lalich ◽  
Rachel Kennedy ◽  
Kristen Williams

Abstract Introduction: Valproic acid (VPA) and its derivatives are highly protein bound with free fraction increasing with dose and serum concentration. Consensus guidelines regarding dose adjustment for hypoalbuminemia are not available. Methods: A literature search was performed using PubMed to identify articles with the following key terms: “valproate,” “valproic acid,” “protein binding,” “albumin,” and “hypoalbuminemia.” We report our findings as well as 5 cases involving pharmacokinetic impact of hypoalbuminemia on valproate. Results: A previously published model for normalizing VPA serum concentration for hypoalbuminemia in patients with epilepsy was compared to results for 5 cases (4 female, 1 male) in which VPA was used for psychiatric illness. Only 1 of the cases had free serum concentrations in the range that would be expected with the model. Free concentrations ranged from 22% to 83% with no clear relationship to other factors (weight, age, serum creatinine, or dose). Female patients with similar albumin had higher free fractions than the 1 male patient. Discussion: Due to the variability in pharmacokinetic impact of hypoalbuminemia, it is important to monitor patients closely for signs of VPA toxicity in cases involving altered albumin levels. It would be prudent to use free serum VPA concentrations when patients experience fluctuations in albumin or have unexpected response to medication.


Dermatology ◽  
2020 ◽  
pp. 1-7
Author(s):  
Aleksandra Batycka-Baran ◽  
Wojciech Baran ◽  
Danuta Nowicka-Suszko ◽  
Maria Koziol-Gałczyńska ◽  
Andrzej Bieniek ◽  
...  

<b><i>Background:</i></b> Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. An important role of innate immune dysregulation in the pathogenesis of HS has been highlighted. S100A7 (psoriasin) is an innate, antimicrobial protein that exerts proinflammatory and chemotactic action. <b><i>Objectives:</i></b> The objective of the study was to investigate serum concentrations of S100A7 in individuals with HS as compared to healthy controls. Further, we evaluated the expression of S100A7 in lesional HS skin as compared to perilesional (clinically uninvolved) HS skin and normal skin. <b><i>Methods:</i></b> Serum concentrations of S100A7 were evaluated with a commercially available ELISA kit. The expression of S100A7 in the skin was assessed using qRT-PCR and immunofluorescence staining. <b><i>Results:</i></b> We found increased expression of S100A7 in lesional HS skin as compared to perilesional HS skin (<i>p</i> = 0.0017). The expression of S100A7 in lesional HS skin was positively associated with serum C-reactive protein concentration and the severity of disease according to Hurley staging. The serum concentration of S100A7 in individuals with HS was decreased as compared to healthy controls and patients with psoriasis. <b><i>Conclusions:</i></b> Upregulated in lesional HS skin, S100A7 may enhance the inflammatory process and contribute to the HS pathogenesis.


1975 ◽  
Vol 48 (3) ◽  
pp. 231-233
Author(s):  
P. Dandona ◽  
D. J. El Kabir ◽  
F. Naftolin ◽  
P. C. B. MacKinnon

1. The effect of long-acting thyroid stimulator (LATS) on the serum luteinizing hormone (LH) levels of the rat in pro-oestrus has been studied. 2. The injection of three out of four LATS-containing immunoglobulin G fractions caused an increase in amounts of serum LH. 3. Adrenalectomy and dexamethasone suppression did not alter this response. 4. Injection of large doses of adrenocorticotrophic hormone did not produce any increase in serum concentrations of LH. 5. It is postulated that LATS may have a direct effect on the release of LH from the pituitary gland.


2019 ◽  
Vol 54 (4) ◽  
pp. 233-240
Author(s):  
Agnieszka Olejnik ◽  
Iwona Bil-Lula ◽  
Anna Krzywonos-Zawadzka ◽  
Łukasz Kozera

Background: Adipose tissue has been recognized as an endocrine organ of considerable complexity, able to secrete adipose-derived factors named adipokines. The secretion of adipokines depends greatly on the volume of body fat, which in turn significantly changes their activity towards a diabetogenic, proinflammatory, and atherogenic pattern. One of the discovered adipokines is dipeptidyl peptidase 4 (DPP4).<br>Objectives: The aim of this preliminary study was to establish an association between serum concentration of DPP4 and obesity at early stage.<br>Material and methods: A total of 32 obese adult volunteers and 40 lean controls were studied. Total cholesterol, triglycerides, HDL (high-density lipoprotein), LDL (low-density lipoprotein) and glucose concentrations were assessed in serum/plasma samples by using commercial tests. Body mass index (BMI) and waist-hip ratio (WHR) were determined. Serum concentrations of DPP4, leptin, visfatin, CRP (C-reactive protein), and TNF-alpha (tumor necrosis factor alpha) were measured using commercial ELISA immunoassay tests.<br>Results: Serum concentrations of DPP4, leptin and visfatin were significantly higher in obese than in lean subjects. The concentration of DPP4 positively correlated with BMI and body mass. Serum CRP and TNF-alpha were increased in obese compared to non-obese, and had a positive correlation with BMI, WHR and body mass.<br>Conclusions: We showed that there is an association between the DPP4, leptin and visfatin concentration in serum and elevated body weight and BMI even at early stage of obesity (I stage of obesity). It suggest the importance of adipose tissue reduction to prevent rise of adipokines levels and further negative metabolic and inflammatory changes.


2016 ◽  
Vol 69 (5) ◽  
Author(s):  
Wasim S El Nekidy ◽  
Maher M El-Masri ◽  
Greg S Umstead ◽  
Michelle Dehoorne-Smith

<p><strong>ABSTRACT</strong></p><p><strong>Background: </strong>Methicillin-resistant <em>Staphylococcus aureus </em>is a leading cause of death in patients undergoing hemodialysis. However, controversy exists about the optimal dose of vancomycin that will yield the recommended pre-hemodialysis serum concentration of 15–20 mg/L.</p><p><strong>Objective: </strong>To develop a data-driven model to optimize the accuracy of maintenance dosing of vancomycin for patients undergoing hemodialysis.</p><p><strong>Methods</strong><strong>: </strong>A prospective observational cohort study was performed with 164 observations obtained from a convenience sample of 63 patients undergoing hemodialysis. All vancomycin doses were given on the floor after completion of a hemodialysis session. Multivariate linear generalized estimating equation analysis was used to examine independent predictors of pre-hemodialysis serum vancomycin concentration.</p><p><strong>Results: </strong>Pre-hemodialysis serum vancomycin concentration was independently associated with maintenance dose (<em>B </em>= 0.658, <em>p </em>&lt; 0.001), baseline pre-hemodialysis serum concentration of the drug (<em>B </em>= 0.492, <em>p </em>&lt; 0.001), and interdialytic interval (<em>B </em>= –2.133, <em>p </em>&lt; 0.001). According to the best of 4 models that were developed, the maintenance dose of vancomycin required to achieve a pre-hemodialysis serum concentration of 15–20 mg/L, if the baseline serum concentration of the drug was also 15–20 mg/L, was 5.9 mg/kg with interdialytic interval of 48 h and 7.1 mg/kg with interdialytic interval of 72 h. However, if the baseline pre-hemodialysis serum concentration was 10–14.99 mg/L, the required dose increased to 9.2 mg/kg with an interdialytic interval of 48 h and 10.0 mg/kg with an interdialytic interval of 72 h.</p><p><strong>Conclusions: </strong>The maintenance dose of vancomycin varied according to baseline pre-hemodialysis serum concentration of the drug and interdialytic interval. The current practice of targeting a pre-hemodialysis concentration of 15–20 mg/L may be difficult to achieve for the majority of patients undergoing hemodialysis.</p><p><strong>RÉSUMÉ</strong></p><p><strong>Contexte : </strong>Les infections à <em>Staphylococcus aureus </em>résistant à la méthicilline comptent parmi les principales causes de mortalité chez les patients traités par hémodialyse. Or, les avis sont partagés quant à la dose optimale de vancomycine qui permet d’atteindre la concentration sérique recommandée de 15–20 mg/L préalablement à l’hémodialyse.</p><p><strong>Objectif : </strong>Mettre au point un modèle guidé par des données afin d’optimiser l’exactitude de la dose d’entretien de vancomycine chez les patients qui subissent une hémodialyse.</p><p><strong>Méthodes : </strong>Une étude de cohorte prospective observationnelle a été menée à partir de 164 observations obtenues d’un échantillon de commodité de 63 patients traités par hémodialyse. Toutes les doses de vancomycine ont été données à l’unité de soins courants après la fin d’une séance d’hémodialyse. Une analyse de régression linéaire multiple par équation d’estimation généralisée a été effectuée pour cerner les variables indépendantes qui permettent de prévoir la concentration sérique de vancomycine préalablement à l’hémodialyse.</p><p><strong>Résultats : </strong>La concentration sérique de vancomycine avant hémodialyse a été associée de façon indépendante à l’intervalle entre deux dialyses (<em>B </em>= –2,133, <em>p </em>&lt; 0,001), à la dose d’entretien (<em>B </em>= 0,658, <em>p </em>&lt; 0,001) et à la concentration sérique initiale du médicament préalablement à l’hémodialyse (<em>B </em>= 0,492, <em>p </em>&lt; 0,001). Selon les quatre meilleurs modèles élaborés, la dose d’entretien de vancomycine nécessaire pour atteindre une concentration sérique de 15–20 mg/L avant hémodialyse, si la valeur initiale était aussi de 15–20 mg/L, était de 5,9 mg/kg pour un intervalle de 48 h entre deux dialyses et de 7,1 mg/kg pour un intervalle de 72 h entre deux dialyses. Or, si la concentration sérique initiale préalablement à l’hémodialyse se situait entre 10 et 14,99 mg/L, la dose necessaire augmentait à 9,2 mg/kg pour un intervalle de 48 h entre deux dialyses et à 10,0 mg/kg pour un intervalle de 72 h écoulé entre deux dialyses.</p><p><strong>Conclusions : </strong>La dose d’entretien de vancomycine variait en fonction de la concentration sérique initiale du médicament préalablement à l’hémodialyse et en fonction de l’intervalle entre deux dialyses. La pratique actuelle voulant qu’on vise une concentration préalable à l’hémodialyse de 15–20 mg/L peut être difficile à respecter chez la majorité des patients subissant une hémodialyse.<strong></strong></p>


2014 ◽  
Vol 19 (3) ◽  
pp. 182-188
Author(s):  
Lea S. Eiland ◽  
Kalyani B. Sonawane

OBJECTIVES: With an increase in vancomycin resistance and the prevalence of obesity in children, alterations of vancomycin dosing regimens may be necessary to achieve target serum concentrations. The primary objective of this study was to describe initial vancomycin dosing with resulting serum concentrations in healthy-weight and overweight/obese children. Secondary objectives include comparing vancomycin dosing regimens of healthy-weight and overweight/obese patients that produced target trough serum concentrations and evaluating the likelihood of attaining target concentrations by patient characteristics. METHODS: This retrospective review evaluated healthy-weight and overweight/obese patients, aged 2 to 18 years, who had vancomycin trough serum concentrations obtained between 2005 and 2010. Vancomycin dosing, initial trough serum concentrations, pharmacokinetic parameters, and patient demographics were collected for analysis. Target trough serum concentrations were defined as 10 to 20 mg/L. RESULTS: The study included 98 patients (48 healthy weight, 50 overweight/obese) of which only 14 patients (14.2%, 6 healthy weight, 8 obese) reached a target trough serum concentration with empiric dosing. No difference was found between the mean daily dosing of vancomycin that produced target trough serum concentrations in healthy-weight or overweight/obese patients (53.63 mg/kg/day vs 51.6 mg/kg/day, respectively). Demographic or clinical characteristics were not found to be associated with the likelihood of target trough serum concentration attainment. CONCLUSIONS: Vancomycin dosing in healthy-weight and overweight/obese pediatric patients did not reach target trough serum concentrations most of the time. In obtaining initial target serum concentrations, no dosing difference was identified for overweight/obese patients compared with healthy-weight patients. Alternate dosing strategies, therapeutic monitoring, and clinical outcomes should continue to be evaluated in this population.


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