Abstract:
AIMS:The pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be inconsistent with the emerging scientific evidence. Limited information is available on the safety profile of these agents in neonates. Our objective was to study the population PK and safety of both drugs, randomly administered in neonates with suspected or confirmed systemic candidiasis. METHODS:Neonates were randomized 1:1 to fluconazole (loading dose 25 mg kg-1 ; maintenance dose 12 mg kg-1 day-1 or 20 mg kg-1 day-1 , respectively, for infants <30 weeks or ≥30 weeks' corrected gestational age) or micafungin (loading dose 15 mg kg-1 day-1 ; maintenance dose 10 mg kg-1 day-1 ). PK samples were taken on treatment days 1 and 5. Population parameters were determined using NONMEM and Monte Carlo simulations performed to reach predefined targets. Clinical and laboratory data, and adverse events were collected up to 36 weeks' corrected gestational age or hospital discharge. RESULTS:Thirty-six neonates were enrolled. The median (range) gestational age was 28.2 (24.1-40.1) and 26.8 (23.5-40.0) weeks for fluconazole and micafungin, respectively. Based on 163 PK samples, the median population clearance (l h-1 kg-1 ) and volume of distribution (l kg-1 ) for fluconazole were: 0.015 [95% confidence interval (CI) 0.008, 0.039] and 0.913, and for micafungin were: 0.020 (95% CI 0.010, 0.023) and 0.354 (95% CI 0.225, 0.482), respectively. The loading dose was well tolerated. No adverse events associated with micafungin or fluconazole were reported. CONCLUSION:Based on Monte Carlo simulations, a loading dose for fluconazole and dosing higher than recommended for both drugs are required to increase the area under the plasma drug concentration-time curve target attainment rate in neonates.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Leroux S,Jacqz-Aigrain E,Elie V,Legrand F,Barin-Le Guellec C,Aurich B,Biran V,Dusang B,Goudjil S,Coopman S,Garcia Sanchez R,Zhao W,Manzoni P,FP7 TINN (Treat Infections in NeoNates) consortium.doi
10.1111/bcp.13628subject
Has Abstractpub_date
2018-09-01 00:00:00pages
1989-1999issue
9eissn
0306-5251issn
1365-2125journal_volume
84pub_type
杂志文章,多中心研究,随机对照试验abstract:AIMS:To ascertain the effects of the Medicines and Healthcare products Regulatory Agency's (MHRA) safety update in June 2010 on the volume of prescribing of quinine and on indices of quinine toxicity. METHODS:We analysed quarterly primary care total and quinine prescribing data for England and quinine prescribing volu...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12130
更新日期:2013-12-01 00:00:00
abstract::1. We have tested the hypothesis that the fall in hepatic mass with age influences the age related increase in sensitivity to warfarin. In 39 otherwise healthy outpatients, aged 50-87 years, stabilised on warfarin for prophylaxis of thromboembolism, age, mean International Normalised Ratio (INR), and mean warfarin dos...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract:AIMS:The aims of the study were to characterize the pharmacokinetics (PK) of selumetinib (AZD6244; ARRY-142886), a mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor in clinical development for various indications, and its N-desmethyl metabolite in healthy volunteers, and evaluate clinically important covariat...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2004-02-01 00:00:00
abstract:AIMS:Helicobacter pylori (H. pylori) eradication rate varies according to the treatment regimen used and other factors, e.g. antimicrobial resistance and patient compliance. The aim of the present study was to evaluate the influence of patient counselling and follow-up on H. pylori eradication rates and to document the...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1991-04-01 00:00:00
abstract::1. We have investigated the effect of repeated s.c. Org 10172 (a low molecular weight heparinoid; Lomoparan) treatment (1000 anti-Xa units twice daily for 5 days) on antipyrine (500 mg orally) metabolism, and the effect of enzyme induction by pentobarbitone (100 mg for 12 days) on the pharmacokinetics and pharmacodyna...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1991.tb05608.x
更新日期:1991-07-01 00:00:00
abstract:AIMS:The goal of this study was to determine the frequencies of important allelic variants in the TPMT, NAT2, GST, SULT1A1 and MDR-1 genes in the Egyptian population and compare them with the frequencies in other ethnic populations. METHODS:Genotyping was carried out in a total of 200 unrelated Egyptian subjects. TPMT...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.01786.x
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:2010-01-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1998-12-01 00:00:00
abstract::The influence of cimetidine pretreatment on the pharmacokinetics of 5-fluorouracil (5FU) has been studied in 15 ambulant patients with carcinoma. Neither pretreatment with a single dose of cimetidine (400 mg) nor with daily treatment at 1000 mg for 1 week altered 5FU pharmacokinetics. Pretreatment with cimetidine for ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02484.x
更新日期:1984-09-01 00:00:00
abstract:AIM:The aim of the study was to simplify the dosing regimen of peginterferon alfa-2a in paediatric patients with chronic hepatitis C. METHODS:A population pharmacokinetic (PK) model was developed using PK data from 14 children aged 2-8 years and 402 adults. Simulations were produced to identify a simplified dosing reg...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12816
更新日期:2016-04-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2004.02259.x
更新日期:2005-02-01 00:00:00
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journal_title:British journal of clinical pharmacology
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13874
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更新日期:2013-11-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb01886.x
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abstract::1. Blood and urine concentrations of the macrolide immunosuppressant FK506 and its metabolites were measured in seven orthotopic liver transplant patients after the first oral dose of FK506 (0.04 +/- 0.02 mg kg-1) used as primary immunosuppressant. A specific h.p.l.c.-MS assay was used, allowing the measurement of par...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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doi:10.1111/j.1365-2125.1983.tb02090.x
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:2004-09-01 00:00:00
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journal_title:British journal of clinical pharmacology
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更新日期:2005-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/bcp.12191
更新日期:2013-09-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:1994-06-01 00:00:00
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journal_title:British journal of clinical pharmacology
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2004-05-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1983-01-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
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更新日期:2014-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-12-01 00:00:00