Evaluation of the drug interaction between intravenous high-dose fluconazole and cyclosporine or tacrolimus in bone marrow transplant patients.
The purpose of this open-label, prospective study was to compare steady state concentrations and clearances of intravenously administered cyclosporine or tacrolimus with and without concomitant high-dose (400 mg/day) fluconazole in allogeneic BMT patients. Twenty-one patients were evaluable. The mean steady state cyclosporine and tacrolimus concentrations without fluconazole were 320.3 and 18.2 ng/ml and increased to 389.2 and 21.2 ng/ml, respectively, after the addition of fluconazole, corresponding to a 21% (P=0.031) and 16% (P=0.125) increase. The mean steady state clearance of cyclosporine and tacrolimus without fluconazole was 6.82 and 1.28 ml/min/kg, which decreased to 5.57 and 1.10 ml/min/kg with fluconazole, corresponding to a 21% (P=0.031) and 16% (P=0.125) decrease, respectively. The 21% difference in the cyclosporine concentration and clearance was not thought to be clinically significant. These results suggest that fluconazole's interaction with cyclosporine or tacrolimus may be a result of fluconazole's inhibition of gut metabolism, resulting in a greater extent of absorption.
Osowski
C L
CL
Emory University Hospital, Atlanta, GA 30322, USA.
Dix
S P
SP
Lin
L S
LS
Mullins
R E
RE
Geller
R B
RB
Wingard
J R
JR
D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004347:Drug Interactions; D015725:Fluconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014184:Transplantation, Homologous
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D015725:Fluconazole; D016559:Tacrolimus