Abstract:
:Lomitapide is a microsomal triglyceride transfer protein inhibitor approved as an adjunctive treatment for adult patients with homozygous familial hypercholesterolemia. Lomitapide is extensively metabolized via cytochrome P450 3A (CYP3A) and is a weak CYP3A inhibitor. Two phase 1 open-label, randomized (1:1), 2-arm drug interaction studies in healthy subjects assessed the effects of atorvastatin and ethinyl estradiol (EE)/norgestimate, both weak CYP3A inhibitors, on lomitapide pharmacokinetics with staggered (separated by 12 hours) or simultaneous administration. All subjects received a single dose of lomitapide (20 mg) in the evening on day 1. Atorvastatin (80 mg once daily, n = 32) or EE/norgestimate (0.035/0.25 mg once daily, n = 32) dosing was initiated on days 11 or 8, respectively, with evening (arm 1) or morning (arm 2) dosing; at steady state (days 15 or 22), a single lomitapide dose was administered; CYP3A inhibitor dosing continued for 6 days. Blood samples for pharmacokinetic analysis were taken until 168 hours postdose. With atorvastatin, lomitapide exposure was increased by approximately 2-fold and 1.3-fold, respectively, with simultaneous and staggered administration, respectively. Simultaneous and staggered EE/norgestimate and lomitapide administration resulted in an approximately 1.3-fold increase in lomitapide exposure. Reductions in lomitapide dose may be required for some patients when administered concomitantly with a weak CYP3A inhibitor.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Patel G,King A,Dutta S,Korb S,Wade JR,Foulds P,Sumeray Mdoi
10.1002/jcph.581subject
Has Abstractpub_date
2016-01-01 00:00:00pages
47-55issue
1eissn
0091-2700issn
1552-4604journal_volume
56pub_type
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