Lack of pharmacokinetic interaction between anidulafungin and tacrolimus.
The safety and pharmacokinetics of anidulafungin coadministered with tacrolimus were investigated using a single-sequence, open-label design. Healthy volunteers received 5 mg tacrolimus orally on days 1 and 13 of the study. Anidulafungin (200 mg) was administered intravenously on day 4, followed by 100-mg doses on days 5 through 13. Key pharmacokinetic parameters, including C(max), AUC, t((1/2)), CL, and V(ss), were derived from concentration-time data. The 90% confidence intervals (CIs) of the ratios of mean pharmacokinetic parameters of anidulafungin plus tacrolimus to each drug alone were well within the 80% to 125% bioequivalence range, indicating no pharmacokinetic interaction. This ratio was 101.6 (90% CI: 92.77-111.22) for tacrolimus AUC(0-infinity) and 107.2 (90% CI: 105.1-109.4) for anidulafungin AUC(ss). The 2 drugs were well tolerated, and no drug-related serious adverse events were reported. Because of its lack of pharmacokinetic interaction with key immunosuppressive agents, anidulafungin is an important option for the prevention and treatment of invasive fungal infections in transplant recipients.
Dowell
James A
JA
Clinical Pharmacology, Pfizer Global Research & Development, 685 3rd Avenue, New York, NY 10017, USA.
Stogniew
Martin
M
Krause
David
D
Henkel
Timothy
T
Damle
Bharat
B
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D004244:Dizziness / Q000139:chemically induced; D004347:Drug Interactions; D054714:Echinocandins; D005221:Fatigue / Q000139:chemically induced; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D053158:Nocturia / Q000139:chemically induced; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D013924:Thrombophlebitis / Q000139:chemically induced
D000935:Antifungal Agents; D054714:Echinocandins; D007166:Immunosuppressive Agents; D010456:Peptides, Cyclic; D000077612:Anidulafungin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase; D016559:Tacrolimus