scholarly journals Initial dose recommendation for sirolimus in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094762
Author(s):  
Xiao Chen ◽  
Dong-Dong Wang ◽  
Hong Xu ◽  
Zhi-Ping Li
Keyword(s):  
Body Weight ◽  
Population Pharmacokinetics ◽  
Initial Dose ◽  
Initial Dosage ◽  
Population Characteristics ◽  
Test Results ◽  
Dosing Regimen ◽  
The Monte Carlo Method ◽  
Laboratory Test Results ◽  
Retrospective Clinical Study

Objective Sirolimus has been used to treat paediatric kaposiform haemangioendothelioma patients. However, there is considerable pharmacokinetic variability among individuals, and it is difficult to develop an initial dosing regimen. The goal of the present study is to recommend an initial sirolimus dose in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics. Methods This was a retrospective clinical study. A population pharmacokinetics model was established and population characteristics, laboratory test results, drug combinations, and pharmacogenomics were considered as potential covariates. The Monte Carlo method was used to simulate the optimal initial dosage. Results The final covariates that affect sirolimus clearance include weight and the CYP3A5 genotype. The initial dosage of sirolimus for individuals with CYP3A5*3/*3 was 0.20 mg/kg split into two doses for 5 to 60 kg body weight. For individuals with CYP3A5*1, the initial dose was 0.23 mg/kg split into two doses for 5 to 30 kg body weight and 0.20 mg/kg split into two doses for 30 to 60 kg body weight. Conclusion The recommendation for the initial sirolimus dose in paediatric kaposiform haemangioendothelioma patients was based on population pharmacokinetics and pharmacogenomics. This study may provide practical value for sirolimus clinical use in paediatric kaposiform haemangioendothelioma patients.

scholarly journals Population Pharmacokinetics and Dosing Optimization of Azithromycin in Children with Community-Acquired Pneumonia

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Yi Zheng ◽  
Shu-Ping Liu ◽  
Bao-Ping Xu ◽  
Zhong-Ren Shi ◽  
Kai Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Population Pharmacokinetics ◽  
Pediatric Patients ◽  
Community Acquired Pneumonia ◽  
Pharmacodynamic Modeling ◽  
Pharmacokinetic Data ◽  
Loading Dose ◽  
Dosing Regimen ◽  
Time Curve ◽  
Dose Strategy

ABSTRACT Azithromycin is extensively used in children with community-acquired pneumonia (CAP). Currently, the intravenous azithromycin is used off-label in children partly due to lacking of pharmacokinetic data. Our objective was to evaluate the population pharmacokinetics (PPK) and optimize dose strategy in order to improve treatment in this distinctive population. This was a prospective, multicenter, open-labeled pharmacokinetic study. Blood samples were collected from hospitalized pediatric patients and concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PPK analysis was conducted using NONMEM software. The pharmacokinetic data from 95 pediatric patients (age range, 2.1 to 11.7 years) were available for analysis. The PPK was best fitted by a two-compartment model with linear elimination. Covariate analysis verified that body weight and alanine aminotransferase (ALT) had significant effects on azithromycin pharmacokinetics, yielding a 24% decrease of clearance in patients with ALT of >40. Monte Carlo simulation showed that for children with normal liver function, a loading-dose strategy (a loading dose of 15 mg/kg of body weight followed by maintenance doses of 10 mg/kg) would achieve the ratio of the area under free drug plasma concentration-time curve over 24 h (fAUC) to MIC90 (fAUC/MIC) target of 3 h in 53.2% of hypothetical patients, using a normative MIC susceptibility breakpoint of 2 mg/liter. For children with ALT of >40, the proposed dose needed to decrease by 15% to achieve comparable exposure. The corresponding risk of overdose for the recommended dosing regimen was less than 5.8%. In conclusion, the PPK of azithromycin was evaluated in children with CAP and an optimal dosing regimen was constructed based on developmental pharmacokinetic-pharmacodynamic modeling and simulation.

New Therapy for Severe Cystic Acne

PEDIATRICS ◽  
1983 ◽  
Vol 72 (2) ◽  
pp. 258-259
Author(s):  
Keyword(s):  
Body Weight ◽  
Retinoic Acid ◽  
Sebaceous Gland ◽  
Skin Surface ◽  
Surface Lipid ◽  
Test Results ◽  
Laboratory Test Results ◽  
Skin Surface Lipid ◽  
Systemic Antibiotics ◽  
Sebum Excretion

Isotretinoin, 13-cis-retinoic acid (Accutane, Hoffmann-LaRoche), is brightening the bleak outlook for adolescents and young adults with nodular, cystic, and conglobate acne—a severe, scarring disease—that has resisted treatment with topical or systemic antibiotics, benzoyl peroxide, retinoic acid, and intralesional corticosteroids. Adolescents with less severe forms of acne who learn about the therapeutic triumphs of isotretinoin in severe recalcitrant nodular and cystic acne may assume that the drug also would be beneficial for them. Pediatricians should inform these adolescents that the drug has not been studied in, found effective for, or labeled for the treatment of typical acne. Patients with multiple, active, deep dermal or subcutaneous cystic and nodular acne lesions are usually given 1 to 2 mg of isotretinoin per kilogram of body weight per day (although dosage as low as 0.05 mg/kg/d has been reported as beneficial), orally, in two divided doses for 15 to 20 weeks or until the cyst count decreases by 70%, if this happens sooner than 15 to 20 weeks. Use of this drug is associated with a reduction in sebaceous gland size and activity (a decrease in sebum excretion by as much as 75% to 90%), with inhibition of sebaceous cell differentiation, and with a reversion to prepubertal skin surface lipid composition. Although isotretinoin is expensive, a course of treatment usually clears the troublesome lesions and a prolonged remission often follows. Side effects and alterations in patients' laboratory test results do occur; these appear to be lessened by reduction in dosage and to be fully reversible when the drug is discontinued.

scholarly journals Population Pharmacokinetics of Abacavir in Pregnant Women

2014 ◽  
Vol 58 (10) ◽  
pp. 6287-6289 ◽  
Author(s):  
Floris Fauchet ◽  
Jean-Marc Treluyer ◽  
Laure-Helene Préta ◽  
Elodie Valade ◽  
Emmanuelle Pannier ◽  
...  
Keyword(s):  
Body Weight ◽  
Pregnant Women ◽  
Population Pharmacokinetics ◽  
Gestational Age ◽  
Population Approach ◽  
Covariate Effect ◽  
Dosing Regimen ◽  
First Time

ABSTRACTFor the first time, a population approach was used to describe abacavir (ABC) pharmacokinetics in HIV-infected pregnant and nonpregnant women. A total of 266 samples from 150 women were obtained. No covariate effect (from age, body weight, pregnancy, or gestational age) on ABC pharmacokinetics was found. Thus, it seems unnecessary to adapt the ABC dosing regimen during pregnancy.

Population pharmacokinetics and dosing optimization of vancomycin in infants, children and adolescents with augmented renal clearance

2021 ◽  
Author(s):  
Cui-Yao He ◽  
Pan-Pan Ye ◽  
Bin Liu ◽  
Lin Song ◽  
John van den Anker ◽  
...  
Keyword(s):  
Body Weight ◽  
Population Pharmacokinetics ◽  
Renal Clearance ◽  
Pharmacokinetic Model ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
Dosing Regimen ◽  
Augmented Renal Clearance ◽  
Vancomycin Dose ◽  
First Order

Augmented renal clearance (ARC) can cause underexposure to vancomycin, thereby increasing the risk of treatment failure. Our objective was to evaluate population pharmacokinetics and optimize the dosing regimen of vancomycin in the pediatric population with ARC. Sparse pharmacokinetic sampling and therapeutic drug monitoring (TDM) data were collected from pediatric patients with ARC treated with vancomycin. A pharmacokinetic model was developed using NONMEM 7.2. The dosing regimen was optimized using Monte Carlo dose simulations. A total of 242 vancomycin serum concentrations from 113 patients (age range 0.4 to 14.9 years, 49 females and 64 males) were available. Mean vancomycin dose was 58.8 mg/kg/day (13.6 mg/kg/dose), and mean vancomycin serum trough concentration was 6.5 mg/L. A one-compartment pharmacokinetic model with first order elimination was developed. Body weight and age were the most significant and positive covariates for clearance and volume of distribution. To the pediatric population with ARC, the current recommended vancomycin dose of 60 mg/kg/day was associated with a high risk of underdosing. To reach the target AUC/MIC of 400-700 in these pediatric patients, the vancomycin dose should be increased to 75 mg/kg/day for infants and children between 1 month and 12 years of age, and 70 mg/kg/day for adolescents between 12 and 18 years of age. In conclusion, a one-compartment pharmacokinetic model with first-order elimination was established with body weight and age as significant covariates. An optimal dosing regimen was developed in pediatric patients with ARC aged 1 month -18 years.

Evaluation of a New Preparation of Urokinase

1973 ◽  
Vol 30 (01) ◽  
pp. 114-122
Author(s):  
C.R.M Prentice ◽  
K.M Rogers ◽  
G.P McNicol
Keyword(s):  
Body Weight ◽  
Maintenance Therapy ◽  
Initial Dose ◽  
Fibrinolytic Activity ◽  
Pharmacological Effect ◽  
Whole Body ◽  
Fibrinolytic Agent ◽  
Thromboplastic Activity

SummaryThe pharmacological effect of a new preparation of urokinase (Leo) has been studied, both in vitro and in six patients suffering from thrombo-embolic disorders. It was a non-toxic, effective fibrinolytic agent if given in sufficient dosage. A regimen consisting of an initial dose of 7,200 ploug units per kg body weight, followed by hourly maintenance therapy with 3,600 ploug units per kg intravenously, gave satisfactory evidence of whole body fibrinolytic activity. The preparation had minor but insignificant thromboplastic activity both when assayed in the laboratory and when given to patients.

Single and repeated testing of growth hormone secretory capacity in hypopituitarism using growth hormone releasing factor

1986 ◽  
Vol 113 (4_Suppl) ◽  
pp. S118-S122 ◽  
Author(s):  
O. BUTENANDT ◽  
M. EMMLINGER ◽  
H. DOERR
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Pituitary Gland ◽  
Bolus Injection ◽  
Hormone Deficiency ◽  
Test Results ◽  
Repeated Testing ◽  
Plasma Growth Hormone ◽  
Once Daily ◽  
Secretory Capacity

Abstract 38 patients with proven growth hormone deficiency (GHD) and 19 children with familial short stature received an iv GRF-bolus injection of 1 ug/kg body weight. Whereas in all control children plasma growth hormone rose significantly (mean of maximal values 36 ng/ml), only 7 out of 38 patients with GHD reached peak values of 8 ng/ml or more. GRF-priming by 1 ug GRF/kg BW given once daily s.c. for 5 days in 19 patients improved the response of the pituitary gland in 11. Thus, following the first GRF test, only 21 % of patients demonstrated function of the pituitary gland whereas 45 % did so when all test results are combined. To evaluate the pituitary function in patients with GHD correctly, GRF tests following a GRF priming period seems to be necessary to reactivate atrophic somatotropic cells of the pituitary gland.

Effect of Ibuprofen on Serum Laboratory Test Results

1983 ◽  
Vol 40 (6) ◽  
pp. 1025-1034
Author(s):  
Carol L. Colvin ◽  
Raymond J. Townsend ◽  
William R. Gillespie ◽  
Kenneth S. Albert
Keyword(s):  
Laboratory Test ◽  
Test Results ◽  
Laboratory Test Results

Quality benchmarking of smartphone laboratory medicine applications: comparison of laboratory medicine specialists’ and non-laboratory medicine professionals’ evaluation

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Snežana Jovičić ◽  
Joanna Siodmiak ◽  
Marta Duque Alcorta ◽  
Maximillian Kittel ◽  
Wytze Oosterhuis ◽  
...  
Keyword(s):  
Information Quality ◽  
Rating Scale ◽  
Laboratory Medicine ◽  
Test Results ◽  
Content Quality ◽  
Laboratory Test Results ◽  
System Usability Scale ◽  
Mobile Health Applications ◽  
Fit For Purpose ◽  
Health Applications

AbstractObjectivesThere are many mobile health applications (apps) now available and some that use in some way laboratory medicine data. Among them, patient-oriented are of the lowest content quality. The aim of this study was to compare the opinions of non-laboratory medicine professionals (NLMP) with those of laboratory medicine specialists (LMS) and define the benchmarks for quality assessment of laboratory medicine apps.MethodsTwenty-five volunteers from six European countries evaluated 16 selected patient-oriented apps. Participants were 20–60 years old, 44% were females, with different educational degrees, and no professional involvement in laboratory medicine. Each participant completed a questionnaire based on the Mobile Application Rating Scale (MARS) and the System Usability Scale, as previously used for rating the app quality by LMS. The responses from the two groups were compared using the Mann-Whitney U test and Spearman correlation.ResultsThe median total score of NLMP app evaluation was 2.73 out of 5 (IQR 0.95) compared to 3.78 (IQR 1.05) by the LMS. All scores were statistically significantly lower in the NLMP group (p<0.05), except for the item Information quality (p=0.1631). The suggested benchmarks for a useful appear: increasing awareness of the importance and delivering an understanding of persons’ own laboratory test results; understandable terminology; easy to use; appropriate graphic design, and trustworthy information.ConclusionsNLMP’ evaluation confirmed the low utility of currently available laboratory medicine apps. A reliable app should contain trustworthy and understandable information. The appearance of an app should be fit for purpose and easy to use.

Sign in / Sign up

Export Citation Format

Share Document