Mould-active azoles: Pharmacokinetics, drug interactions in neutropenic patients

Current Opinion in Infectious Diseases

Volumn 20, Issue 6, 2007, Pages 579-586

  Gubbins, Paul O ^a  

^a UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

Author keywords

Drug interactions; Itraconazole; Posaconazole; Voriconazole

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; AMINOTRANSFERASE; ANTACID AGENT; ANTINEOPLASTIC AGENT; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; BREAST CANCER RESISTANCE PROTEIN; CALCINEURIN INHIBITOR; CORTICOSTEROID; CYCLOSPORIN; CYCLOSPORIN A; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; DOXORUBICIN; HISTAMINE H2 RECEPTOR ANTAGONIST; ITRACONAZOLE; METHYLPREDNISOLONE; POSACONAZOLE; PREDNISOLONE; PROTON PUMP INHIBITOR; PYRROLE DERIVATIVE; RAPAMYCIN; TACROLIMUS; UNINDEXED DRUG; VINBLASTINE; VINCA ALKALOID; VINCRISTINE; VORICONAZOLE;

ABDOMINAL DISTENSION; ABDOMINAL PAIN; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; AMINOTRANSFERASE BLOOD LEVEL; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ASPERGILLOSIS; BILIRUBIN BLOOD LEVEL; CONSTIPATION; DIARRHEA; DISTRIBUTION VOLUME; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG MONITORING; DRUG PENETRATION; DRUG SAFETY; DRUG SUBSTITUTION; DRUG WITHDRAWAL; FOOD DRUG INTERACTION; GASTROINTESTINAL SYMPTOM; HUMAN; HYPONATREMIA; ILEUS; INAPPROPRIATE VASOPRESSIN SECRETION; LIVER TOXICITY; LOW BACK PAIN; MOULD; MUCOSA INFLAMMATION; MUSCLE WEAKNESS; MYCOSIS; NEUROPATHY; NEUROTOXICITY; NEUTROPENIA; NONHUMAN; PARESTHESIA; PATIENT COMPLIANCE; REVIEW; SEIZURE; SENSORY DYSFUNCTION; SIDE EFFECT; SYSTEMIC DISEASE; VISUAL DISORDER; VOMITING;

ANTIFUNGAL AGENTS; AZOLES; DRUG INTERACTIONS; FUNGI; HUMANS; MYCOSES; NEUTROPENIA;

EID: 35848965204     PISSN: 09517375     EISSN: None     Source Type: Journal    
DOI: 10.1097/QCO.0b013e3282f1be91     Document Type: Review

References (40)

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38. Sasone-Parsons A, Krishna G, Martinho M, et al. Effect of oral posaconazole on the pharmacokinetics of cyclosporine and tacrolimus. Pharmacotherapy 2007; 27:825-834. This paper is notable in that it provides important data regarding the interaction between posaconazole and both cyclosporine and tacrolimus. The paper is also important because it illustrates that even drugs that are minimally metabolized by CYP3A4 can still be potent inhibitors of this important enzyme. Often this distinction is missed or confused, and clinicians can mistakenly think that as posaconazole is a poor CYP3A4 substrate it will be relatively devoid of drug interactions.
39. Krishna G, Sasone-Parsons A, Kantesaria B, Mant T. Evaluation of the pharmacokinetics of posaconazole and rifabutin following co-administration to healthy men. Curr Med Res Opin 2007; 23:545-552. This paper is notable in that it provides important data regarding the interaction between posaconazole and rifabutin. The study demonstrates that although it is minimally metabolized, it inhibits rifabutin metabolism, which in turn accumulates and induces posaconazole metabolism. Even with the bidirectional nature of the interaction, the magnitude of the effects is surprising, and raises the question as to whether the interaction also involves phase II enzymes.
40. Krishna G, Sasone-Parsons A, Kantesaria B. Drug interaction assessment following concomitant administration of posaconazole and phenytoin in healthy men. Curr Med Res Opin 2007; 23:1415-1422. This paper is notable in that it provides important data regarding the interaction between posaconazole and phenytoin. The study demonstrates that cytochrome P450 inducers can also induce phase II enzymes such as UGT. This may partly explain interactions with the mould-inactive azole fluconazole, which also interacts with the UGT pathway.