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Because anidulafungin 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 anidulafungin is approved for the treatment of invasive candidiasis in adult non-neutropenic patients, dosing guidelines for anidulafungin in (morbidly) obese patients are not available. Subsequently, the pharmacokinetic profile of anidulafungin (as well as other echinocandins) in this specific patient population is still largely unknown. During endoscopic gastric bypass surgery, patients are more prone to various kinds of infection, justifying the prophylactic use of anidulafungin in this specific cohort of patients.
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 anidulafungin (besides standard anti-bacterial prophylaxis) and a PK-curve will be drawn. These PK-values can then be compared to the pharmacokinetics in a normal-weight group.
All obese patients with a BMI ≥ 40 kg/m2 undergoing endoscopic gastric bypass surgery who receive a prophylactic single dose of 100 mg anidulafungin will be included in the analysis. A PK curve will be determined after administration of anidulafungin at t=0.5, 1, end of infusion, 2, 4, 6, 8, 10, 12, 24, and 48 and (if feasible) 72 hours post infusion (n=12 samples). Blood samples (4 mL) on PK days will be taken to obtain at least 2.0 mL of plasma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anidulafungin 100 mg single dose | Experimental | 100 mg single dose anidulafungin pre-surgery (gastric bypass) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anidulafungin 100mg single dose iv | Drug | Anidulafungin 100mg single dose iv pre-surgery (gastric bypass) |
|
| Measure | Description | Time Frame |
|---|---|---|
| anidulafungin area under the curve | The primary outcome measurement will be the area under the plasma concentration-time curve (AUC) from time 0 to infinitive (inf) post infusion (AUC0- inf) value of anidulafungin. This will be determined by use of the log-linear trapezoidal rule. Peak plasma concentrations (Cmax) will be directly observed from the data. The elimination rate constant will be determined by linear regression of the terminal points of the log-linear plasma concentration time curve. Clearance (CL) will be calculated as dose/AUC0- inf. | 0-72 h after single dose |
| Measure | Description | Time Frame |
|---|---|---|
| Predict long-term exposure after repeated dosing by using a pharmacokinetic model of anidulafunign in obese patients by using AUC(0-inf), Cmax, elimination half-life and clearance. | Simulate pharmacokinetics of anidulafungin after obtaining all plasma concentrations using modeling software to predict long-term exposure. For this, area under the plasma concentration-time curve (AUC) from time 0 to infinitive (inf) post infusion (AUC0- inf), peak plasma concentration (Cmax), elimination half-life and clearance values of anidulafungin will be used (as calculated in outcome measure 1). The PK curve of day 1-3 will serve to calculate these values. |
| Measure | Description | Time Frame |
|---|---|---|
| adverse events | adverse events will be collected and reported | 0-72 h after dosing |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Roger JM Brüggemann, PharmD, PhD | Radboud University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud University Medical Center | Nijmegen | Gelderland | Netherlands | |||
| St. Antonius hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27142114 | Result | Lempers VJ, van Rongen A, van Dongen EP, van Ramshorst B, Burger DM, Aarnoutse RE, Knibbe CA, Bruggemann RJ. Does Weight Impact Anidulafungin Pharmacokinetics? Clin Pharmacokinet. 2016 Oct;55(10):1289-1294. doi: 10.1007/s40262-016-0401-8. |
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| ID | Term |
|---|---|
| D009767 | Obesity, Morbid |
| ID | Term |
|---|---|
| D009765 | Obesity |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
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| ID | Term |
|---|---|
| D000077612 | Anidulafungin |
| ID | Term |
|---|---|
| D054714 | Echinocandins |
| D010456 | Peptides, Cyclic |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| PK curve on day 1-3 |
| Nieuwegein |
| Netherlands |
| D009750 |
| Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |