Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial.


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.


Br J Clin Pharmacol


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.




Has Abstract


2018-09-01 00:00:00












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    pub_type: 临床试验,杂志文章


    authors: Lees KR,Reid JL

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  • Anti-hypertensive dose-response effects of nicardipine in stable essential hypertension.

    abstract::The dose-response effects of oral nicardipine on the systemic blood pressure were examined in 54 patients with uncomplicated essential hypertension (DBP greater than or equal to 100 mm Hg). The study was designed in four sequential stages. A 2 week single-blind placebo run-in period was followed by dose titration with...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章


    authors: Taylor SH,Frais MA,Lee P,Verma SP,Jackson N,Silke B

    更新日期:1985-01-01 00:00:00

  • Determinants of mercaptopurine toxicity in paediatric acute lymphoblastic leukemia maintenance therapy.

    abstract:AIMS:6-mercaptopurine (6-MP) is used in the treatment of childhood acute lymphoblastic leukaemia (ALL). Its red blood cell (RBC) metabolite concentrations (6-thioguanine [6-TGN] and 6-methylmercaptopurine nucleotides [6-MMPN]) are related to drug response. We investigated the impact of non-genetic covariates and pharma...

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    pub_type: 杂志文章


    authors: Adam de Beaumais T,Fakhoury M,Medard Y,Azougagh S,Zhang D,Yakouben K,Jacqz-Aigrain E

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  • The pharmacokinetics of endralazine in essential hypertensives and in normotensive subjects.

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    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Meredith PA,Elliott HL,McSharry DR,Kelman AW,Reid JL

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    abstract:AIMS:To evaluate the electroencephalographic (EEG) effects, blood concentrations, vehicle irritation and dose-effect relationships for diazepam administered nasally. METHODS:The study had a cross-over design with eight healthy volunteers (one drop out). It consisted of four legs with four different administrations: in...

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    pub_type: 临床试验,杂志文章,随机对照试验


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  • Co-prescribing of SSRIs and TCAs in Australia: how often does it occur and who is doing it?

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    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: McManus P,Mant A,Mitchell P,Birkett D,Dudley J

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  • Pharmacokinetics of piroximone after oral and intravenous administration to patients with renal insufficiency.

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    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Fauvel JP,Bernard N,Laville M,Pozet N,Sassard J,Zech PY

    更新日期:1995-02-01 00:00:00

  • Adverse drug reactions - examples of detection of rare events using databases.

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    journal_title:British journal of clinical pharmacology

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    authors: Chan EW,Liu KQ,Chui CS,Sing CW,Wong LY,Wong IC

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    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Posner J,Cohen AF,Land G,Winton C,Peck AW

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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


    authors: Lötsch J,Mohammadian P,Hummel T,Florin S,Brune K,Geisslinger G,Kobal G

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  • Experience with labetalol in hypertension.

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    authors: Bolli P,Waal-Manning J,Wood AJ,Simpson FO

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    journal_title:British journal of clinical pharmacology

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    journal_title:British journal of clinical pharmacology

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    authors: Adebayo GI,Mabadeje AF

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  • Comparative effects of lisinopril and losartan on insulin sensitivity in the treatment of non diabetic hypertensive patients.

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    authors: Fogari R,Zoppi A,Corradi L,Lazzari P,Mugellini A,Lusardi P

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    authors: Greenblatt DJ,Divoll M,Puri SK,Ho I,Zinny MA,Shader RI

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    authors: Spahn H,Kirch W,Mutschler E,Ohnhaus EE,Kitteringham NR,Lögering HJ,Paar D

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    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Choonara I,Lawrence A,Michalkiewicz A,Bowhay A,Ratcliffe J

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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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    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验


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    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Sodha RJ,Schneider H

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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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    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章


    authors: Paxton JW,Briant RH

    更新日期:1984-11-01 00:00:00