OBJECTIVE: We sought to quantify the influence of the CYP3A inhibitor erythromycin on the pharmacokinetics of everolimus, a CYP3A substrate. METHODS: This was a two-period, single-sequence, crossover study in 16 healthy subjects. In period 1, subjects received the reference treatment of a single 2-mg dose of everolimus. In period 2, they received the test treatment of erythromycin 500 mg three times daily for a total of 9 days and a single 2-mg dose of everolimus coadministered on the fifth day of erythromycin therapy. The test/reference ratio and 90% confidence interval (CI) were derived for everolimus C (max) and AUC. RESULTS: During erythromycin coadministration, everolimus C (max) increased 2.0-fold (90% CI, 1.8-2.3) from 20+/-5 ng/ml to 40+/-10 ng/ml. Everolimus AUC increased 4.4-fold (90% CI, 3.5-5.4) from 116+/-37 ng h/ml to 524+/-225 ng h/ml. Everolimus half-life was prolonged by 39% from 32+/-6 h to 44+/-6 h. Erythromycin predose concentrations were not changed after single-dose administration of everolimus. CONCLUSION: Multiple-dose erythromycin increased single-dose everolimus blood levels by an average 4.4-fold (range, 2.0-12.6). During erythromycin treatment, a compensatory everolimus dose reduction should be made guided by everolimus therapeutic drug monitoring.
RCT Entities:
OBJECTIVE: We sought to quantify the influence of the CYP3A inhibitor erythromycin on the pharmacokinetics of everolimus, a CYP3A substrate. METHODS: This was a two-period, single-sequence, crossover study in 16 healthy subjects. In period 1, subjects received the reference treatment of a single 2-mg dose of everolimus. In period 2, they received the test treatment of erythromycin 500 mg three times daily for a total of 9 days and a single 2-mg dose of everolimus coadministered on the fifth day of erythromycin therapy. The test/reference ratio and 90% confidence interval (CI) were derived for everolimus C (max) and AUC. RESULTS: During erythromycin coadministration, everolimus C (max) increased 2.0-fold (90% CI, 1.8-2.3) from 20+/-5 ng/ml to 40+/-10 ng/ml. Everolimus AUC increased 4.4-fold (90% CI, 3.5-5.4) from 116+/-37 ng h/ml to 524+/-225 ng h/ml. Everolimus half-life was prolonged by 39% from 32+/-6 h to 44+/-6 h. Erythromycin predose concentrations were not changed after single-dose administration of everolimus. CONCLUSION: Multiple-dose erythromycin increased single-dose everolimus blood levels by an average 4.4-fold (range, 2.0-12.6). During erythromycin treatment, a compensatory everolimus dose reduction should be made guided by everolimus therapeutic drug monitoring.
Authors: John M Kovarik; Helio Tedesco; Julio Pascual; Giovanni Civati; Marie-Noelle Bizot; Johanna Geissler; Heinz Schmidli Journal: Ther Drug Monit Date: 2004-10 Impact factor: 3.681
Authors: Thorir D Bjornsson; John T Callaghan; Heidi J Einolf; Volker Fischer; Lawrence Gan; Scott Grimm; John Kao; S Peter King; Gerald Miwa; Lan Ni; Gondi Kumar; James McLeod; Scott R Obach; Stanley Roberts; Amy Roe; Anita Shah; Fred Snikeris; John T Sullivan; Donald Tweedie; Jose M Vega; John Walsh; Steven A Wrighton Journal: J Clin Pharmacol Date: 2003-05 Impact factor: 3.126
Authors: C S Lancaster; G H Bruun; C J Peer; T S Mikkelsen; T J Corydon; A A Gibson; S Hu; S J Orwick; R H J Mathijssen; W D Figg; S D Baker; A Sparreboom Journal: Clin Pharmacol Ther Date: 2012-09-19 Impact factor: 6.875
Authors: Dipti K Pawaskar; Robert M Straubinger; Gerald J Fetterly; Bonnie H Hylander; Elizabeth A Repasky; Wen W Ma; William J Jusko Journal: Cancer Chemother Pharmacol Date: 2013-03-03 Impact factor: 3.333
Authors: Yuanyuan Wang; Muh Akbar Bahar; Anouk M E Jansen; Janwillem W H Kocks; Jan-Willem C Alffenaar; Eelko Hak; Bob Wilffert; Sander D Borgsteede Journal: J Antimicrob Chemother Date: 2019-10-01 Impact factor: 5.790
Authors: Mathieu S Bolhuis; Prashant N Panday; Arianna D Pranger; Jos G W Kosterink; Jan-Willem C Alffenaar Journal: Pharmaceutics Date: 2011-11-18 Impact factor: 6.321