Pharmacokinetics of Caspofungin in Burn Patients

The aim of this investigation is to investigate pharmacokinetics of caspofungin in burn patients after a single usual dose (70 mg i.v.). Blood samples are drawn just before administration and 0.25, 0.5,1 1.5, 3, 6, 12, 24, 48, 72, 96 and 120 hours after administration. Caspofungin plasma concentrations are measured by liquid-chromatography spectrometry mass tandem.The primary end-points are :

• area under the curve of caspofungin plasma concentrations over 24 hours
• mean peak level and trough concentration (24 hours after dosing)

The secondary end-points are :

• mean total clearance
• mean distribution volume These parameters will be compared to those usually observed in non burn patients. The optimal dose in burn patients is the dose achieving an exposure similar to that in non burn patients.

Inclusion criteria

• 18 - 60 years old
• burn surface : 20-60% total body surface area
• delay of injury time : 8-15 days
• lack of fungal infection
• delay of hospitalization : > 5 days
• written informed consent
• last biological picture in 24 hours before inclusion

Exclusion criteria

• survival inferior to 5 days
• surgical intervention planned in the next five days following inclusion
• moderate or severe hepatic impairment according to Child Plug B > 9
• pregnancy
• allergy to caspofungin or excipients (saccharose, mannitol and frozen acetic acid)
• patient already included in other study
• concomitant administration of CYP450 inducers : rifampicin, efavirenz, phenobarbital, phenytoin, carbamazepine
• withdrawal of consent
• event (during the first 48 hours following administration) susceptible to modify pharmacokinetic parameters
• Investigator decision
• no social security insurance