PK/PD of Caspofungin in Children Severe Infection

Study Overview
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Brief Summary
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Caspofungin is an anti-fungal drug mainly metabolized by the liver. The pathophysiological status of children with severe infection will affect the metabolism of caspofungin in the body especially in the case of liver dysfunction. There is little metabolism of caspofungin through the kidney and continuous renal replacement therapy and renal function have little influence on the pharmacokinetics of caspofungin. The study aim to investigate PK/PD of caspofungin in children with specific pathophysiological conditions, such as liver insufficiency, hypoproteinemia, ECMO treatment, or sepsis.

Detailed Description
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The current international recommended dose of caspofungin is 70 mg per square metre for load for children who is older than three months of age, followed by 50 mg per square metre for maintenance. For newborns and infants younger than 3 months of age，25 mg per square metre is also recommended. Whether such a recommended dose can achieve an ideal PK/PD target in children with liver insufficiency, hypoproteinemia, ECMO treatment, or severe infection is still lacking in sufficient clinical data. The objective of this study is to investigate PK/PD of caspofungin in children with specific pathophysiological conditions, such as liver insufficiency, hypoproteinemia, ECMO treatment, or sepsis. Blood sampling time points of caspofungin are listed as follow: Before administration (0 min); 1 h, 2 h, 4 h, 8 h , 12 h and 24 h after administration. The concentration of caspofungin in whole blood will be analyzed at Huashan Hospital of Fudan University.

Official Title
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Pharmacokinetics and Pharmacodynamics of Caspofungin in Children Severe Infection

Conditions
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Pharmacokinetics, Infection, Fungal

Intervention / Treatment
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* Drug: Caspofungin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children receiving caspofungin in pediatric intensive care unit Exclusion Criteria: No Informed Consent signed Participate in other clinical trials

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Treatment group<br>Children treated with caspofungin in the pediatric intensive care unit | Drug: Caspofungin<br>* For children 3 months of age, the recommended dose is 70 mg/m2 for load and then 50 mg/m2 for maintenance, intravenous injection, once daily up to 5 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) Pharmacokinetic Parameter | Time to reach the maximum plasma concentration (Tmax) after administrations of a single dose and multiple doses of the study drug | Day 1-5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax: Maximum Observed Plasma Concentration Pharmacokinetic Parameter | Maximum observed plasma concentration (Cmax) is the peak plasma concentration after administrations of a single dose and multiple doses of the study drug | Day 1-5 | 
| AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Pharmacokinetic Parameter | Area under the plasma concentration-time curve from time 0 to infinity after administration of a single dose of the study drug. | Day1-5 | 
| AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Pharmacokinetic Parameter | Area under the curve from 0 to 24 hours after administrations of a single dose and multiple doses of the study drug. | Day1-5 | 
| Terminal Phase Elimination Half-life (T1/2) Pharmacokinetic Parameter | Time required for half of the drug to be eliminated from the plasma after administration of a single dose of the study drug. | Day1-5 |