PMID- 20811346
OWN - NLM
STAT- MEDLINE
DCOM- 20101020
LR  - 20181211
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 88
IP  - 4
DP  - 2010 Oct
TI  - Potential for pharmacokinetic interactions between ambrisentan and cyclosporine.
PG  - 513-20
LID - 10.1038/clpt.2010.120 [doi]
AB  - Ambrisentan (ABS), approved for the treatment of pulmonary arterial hypertension 
      and administered as an oral dose once daily, is an ET(A)-selective endothelin 
      receptor antagonist (ERA) and a potential substrate for cytochrome P450 (CYP) 
      3A4, organic anion-transporting polypeptide (OATP), and P-glycoprotein (P-gp). 
      Cyclosporin A (CsA), an inhibitor of CYP3A4, P-gp, and OATP, may be used 
      concomitantly with ABS. In this open-label, parallel-treatment study, 28 healthy 
      subjects received steady-state ABS (5 mg q.d.) either alone or with steady-state 
      CsA (100-150 mg b.i.d.), and 24 other subjects received steady-state CsA either 
      alone or with steady-state ABS. In the presence of CsA, ABS maximum plasma 
      concentration (C(max)) increased 1.5-fold, and area under the plasma 
      concentration-time curve (AUC)(0-tau) increased twofold. Marginal increases were 
      observed for CsA C(max) (906 vs. 1,014 ng/ml) and AUC(0-tau) (3.05 vs. 3.37 
      microg.h/ml) in the presence of ABS. Frequent adverse events (AEs) were headache and 
      gastrointestinal disorders. The addition of ABS to steady-state CsA appeared less 
      tolerable as compared with the addition of CsA to steady-state ABS. A maximum ABS 
      dose of 5 mg is recommended if it is coadministered with CsA. No change in CsA 
      dose is recommended if it is coadministered with ABS.
FAU - Spence, R
AU  - Spence R
AD  - Gilead Sciences, Inc., Boulder, Colorado, USA.
FAU - Mandagere, A
AU  - Mandagere A
FAU - Richards, D B
AU  - Richards DB
FAU - Magee, M H
AU  - Magee MH
FAU - Dufton, C
AU  - Dufton C
FAU - Boinpally, R
AU  - Boinpally R
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100901
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Cytochrome P-450 CYP3A Inhibitors)
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Organic Anion Transporters)
RN  - 0 (Phenylpropionates)
RN  - 0 (Pyridazines)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - EC 1.14.14.55 (CYP3A4 protein, human)
RN  - HW6NV07QEC (ambrisentan)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors
MH  - Adult
MH  - Antihypertensive Agents/adverse effects/pharmacokinetics/*pharmacology
MH  - Area Under Curve
MH  - Cyclosporine/adverse effects/pharmacokinetics/*pharmacology
MH  - Cytochrome P-450 CYP3A
MH  - Cytochrome P-450 CYP3A Inhibitors
MH  - Drug Interactions
MH  - *Endothelin Receptor Antagonists
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/pharmacokinetics/*pharmacology
MH  - Male
MH  - Organic Anion Transporters/antagonists & inhibitors
MH  - Phenylpropionates/adverse effects/pharmacokinetics/*pharmacology
MH  - Pyridazines/adverse effects/pharmacokinetics/*pharmacology
EDAT- 2010/09/03 06:00
MHDA- 2010/10/21 06:00
CRDT- 2010/09/03 06:00
PHST- 2010/09/03 06:00 [entrez]
PHST- 2010/09/03 06:00 [pubmed]
PHST- 2010/10/21 06:00 [medline]
AID - clpt2010120 [pii]
AID - 10.1038/clpt.2010.120 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2010 Oct;88(4):513-20. doi: 10.1038/clpt.2010.120. Epub 2010 
      Sep 1.