A pharmacological rationale for improved everolimus dosing in oncology and transplant patients.
Br J Clin Pharmacol
; 84(7): 1575-1586, 2018 07.
Article
in En
| MEDLINE
| ID: mdl-29574974
ABSTRACT
AIMS:
Everolimus is a drug from the class of mammalian target of rapamycin inhibitors used for both immunosuppressant and oncological indications. We postulate that there is room for improvement of dosing, as the optimal immunosuppressive dose in calcineurin-free regimens is unknown and since the once daily dosing regimen for oncological indications is often associated with treatment-limiting toxicity.METHODS:
We developed a mechanistic population pharmacokinetic model for everolimus in cancer and transplant patients and explored alternative dosing regimens.RESULTS:
We found that formulation did not influence bioavailability and that use of >20 mg prednisolone daily increased everolimus clearance. In transplant patients, the approved dose of 0.75-1 mg twice daily (BID) results in subtherapeutic trough levels (<6 µg l-1 ) and that a higher starting dose of 2.25-3 mg BID is required.CONCLUSION:
For oncological indications, our results encourage the investigation of dosing everolimus 3.75 mg BID in terms of superiority in safety and noninferiority in efficacy.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antineoplastic Combined Chemotherapy Protocols
/
Everolimus
/
Graft Rejection
/
Immunosuppressive Agents
/
Neoplasms
Type of study:
Clinical_trials
Language:
En
Journal:
Br J Clin Pharmacol
Year:
2018
Type:
Article
Affiliation country:
Netherlands