Drug-drug interaction between voriconazole and tacrolimus. Healthy volunteers.
Conditions
Interventions
Group 1: In this pharmacokinetic interaction study, four single doses of tacrolimus 3 mg are administered orally.
Arm 1: Sequence: Prograf, Envarsus, Prograf + Voriconazole, Envarsus + Voriconazole.
G
Sponsors
Universität Heidelberg, Medizinische Fakultät
Eligibility
Sex/Gender
Male
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Male Caucasian 18 to = 40 kg. Good state of health (physically and mentally). Known CYP2C19 and CYP3A5 genotype or participation in genotyping study (K093). No clinically relevant findings in any of the investigations of the screening visit. Agreement to abstain from St. John’s wort (Hypericum perforatum L.) during the time of the trial. Agreement to follow specified dietary requirements (e.g. citrus products, especially grapefruit are not allowed) starting one week before each trial day. Agreement to follow specified contraceptive measures. Able to communicate well with the investigator, to understand and comply with the requirements of the trial. Voluntarily signed informed consent after full explanation of the trial to the participant.
Exclusion criteria
Exclusion criteria: Intake of a substance known to induce or inhibit drug metabolizing enzymes or drug transporters within a period of less than 10 times the respective elimination half-life or two weeks, whatever is longer. Any physical disorder that could interfere with the participant’s safety during the clinical trial or with the trial objectives. Any acute or chronic illness or clinically relevant finding in the pre-trial examination, especially any condition known or expected to modify absorption, distribution, metabolism, or excretion of the drug under investigation. CYP2C19 poor metaboliser genotype. QTcF > 440 ms. Regular smoking. Excessive alcohol drinking (more than approximately 20 g/d alcohol). Any participation in an interventional clinical trial within the last month before inclusion. Blood donation within 8 weeks before the first trial day. Haemoglobin < 11 g/dl. Known intolerance to tacrolimus, midazolam, voriconazole, or further ingredients of the administered brands.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in tacrolimus exposition (AUC) due to voriconazole. Comparison of inhibition by voriconazole after administration of two different tacrolimus preparations (Envarsus® and Prograf®). | — |
Secondary
| Measure | Time frame |
|---|---|
| Factors that may be associated with the individual degree of the drug-drug interaction (e.g. CYP3A phenotype, rs776746 polymorphism). Relationship between tacrolimus concentrations and PD markers of tacrolimus effects. | — |
Countries
Germany
Contacts
Public ContactDavid Czock
Universitätsklinikum Heidelberg, Abteilung Klinische Pharmakologie und Pharmakoepidemiologie
Outcome results
None listed