Micafungin Pharmacokinetics in Obese Patients
Micafungin Pharmacokinetics in Obese Patients
Because micafungin is generally well tolerated and appears to have limited interaction with
 other drugs, it is a potential important agent in the treatment of invasive fungal
 infections. Although micafungin is approved for the treatment of invasive candidiasis, dosing
 guidelines for micafungin in (morbidly) obese patients are not available. Subsequently, the
 pharmacokinetic profile of micafungin (as well as other echinocandins) in this specific
 patient population is still largely unknown.

 To build a valid pharmacokinetic model, obese patients with a BMI ≥ 40 undergoing endoscopic
 gastric bypass surgery will receive a single dose of 100 mg or 200mg micafungin (besides
 standard anti-bacterial prophylaxis) and samples for a pharmacokinetic curve will be taken.
 These PK-values can then be compared to the PK in a normal-weight group which will receive
 100mg micafungin
Obese patients with a BMI ≥ 40 kg/m2 undergoing endoscopic gastric bypass surgery will
 receive a 100 mg or a 200mg dose of micafungin. A PK curve will be determined after
 administration at t=0.5, 0.95, 1.25, 1.5, 2, 4, 8, 12, 24, and (if feasible) 48 hours post
 infusion. Blood samples (4 mL) on PK days will be taken to obtain at least 2.0 mL of plasma.
Inclusion Criteria

 1. Subjects BMI:

 -  obese groups: subject must have a BMI > 40 kg/m2 at the time of inclusion,

 -  non-obese group: subject must have a BMI ≥18.5 and < 25kg/m2 at the time of
 inclusion.

 2. Subject is at least 18 of age on the day of screening and not older than 65 years of
 age on the day of dosing;

 3. If a woman, is neither pregnant nor able to become pregnant and is not nursing an
 infant;

 4. Subject is able and willing to sign the Informed Consent before screening evaluations.

 For the non-obese subjects the following additional exclusion criteria apply:

 5. Subject is in good age-appropriate health condition as established by medical history,
 physical examination, electrocardiography, results of biochemistry, hematology and
 urinalysis testing within 4 weeks prior to study drug administration. Results of
 biochemistry, hematology and urinalysis testing should be within the laboratory's
 reference ranges. If laboratory results are not within the reference ranges, the
 subject is included based on the investigator's judgment that the observed deviations
 are not clinically relevant. This should be clearly recorded;

 6. Subject has a normal blood pressure and pulse rate, determined by the investigator;

 7. Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at
 least 3 months prior to study drug administration.

 Exclusion Criteria:

 1. Documented history of sensitivity to medicinal products or excipients similar to those
 found in the micafungin preparation;

 2. History of, or known abuse of drugs, alcohol or solvents (up until a maximum of three
 months before study drug administration);

 3. Inability to understand the nature of the trial and the procedures required;

 4. Use of medication that has known interaction with study drug as determined by the
 investigator up to 4 weeks prior to study drug administration.

 For the non-obese subjects the following additional exclusion criteria apply:

 5. Evidence of organ dysfunction or any clinically significant deviation from normal in
 physical examination, vital signs or clinical laboratory determinations;

 6. Clinical relevant liver enzymes (alkaline phosphatase, alanine aminotransferase,
 aspartate transaminase) abnormalities at screening;

 7. Donation of blood or plasma to a blood bank or in a clinical study (except a screening
 visit) within 4 weeks prior to study drug administration;

 8. Blood transfusion within 8 weeks prior to study drug administration;

 9. Inability to be venipunctured and/or tolerate venous access;

 10. Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular
 disorders, neurological disorders (especially seizures and migraine), psychiatric
 disorders, gastro-intestinal disorders, renal disorders, hepatic disorders (Child-Pugh
 B or C), hormonal disorders (especially diabetes mellitus), coagulation disorders;

 11. Any other sound medical, psychiatric and/or social reason as determined by the
 investigator.