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Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin: no clinically relevant drug-drug interactions.
J Clin Pharmacol. 2010 Oct; 50(10):1188-201.JC

Abstract

Dalcetrapib targets cholesteryl ester transfer protein and increases high-density lipoprotein cholesterol (HDL-C) levels. It is in clinical development for the prevention of cardiovascular events and will likely be used in combination with standard of care, including statins. Three crossover studies in healthy males investigated the pharmacokinetic drug-drug interaction potential of 900 mg dalcetrapib and statins: two 3-period studies (dalcetrapib plus pravastatin or rosuvastatin) and a 2-period study (dalcetrapib plus simvastatin). Effect on lipids and safety were secondary end points. The 900 mg dose investigated is higher than the 600 mg dose currently being investigated in Phase III. Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin was not associated with significant increases in statin exposure except for a 26% increase in rosuvastatin C(max) (90% CI 1.088 to 1.468) but not AUC(0-24) (90% CI 0.931 to 1.085). Dalcetrapib AUC(0-24) and C(max) were not significantly altered by coadministration with pravastatin, and were significantly lower when dalcetrapib was coadministered with rosuvastatin or simvastatin compared with dalcetrapib alone. The HDL-C increase with dalcetrapib was not compromised by coadministration with statins, and reduction in low-density lipoprotein cholesterol with dalcetrapib coadministered with statins was greater than with statins alone. Dalcetrapib alone and coadministered with statins was generally well tolerated.

Authors+Show Affiliations

Bldg. 663, office 2139, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland. michael.derks@roche.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20489031

Citation

Derks, Michael, et al. "Coadministration of Dalcetrapib With Pravastatin, Rosuvastatin, or Simvastatin: No Clinically Relevant Drug-drug Interactions." Journal of Clinical Pharmacology, vol. 50, no. 10, 2010, pp. 1188-201.
Derks M, Abt M, Phelan M, et al. Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin: no clinically relevant drug-drug interactions. J Clin Pharmacol. 2010;50(10):1188-201.
Derks, M., Abt, M., Phelan, M., Turnbull, L., Meneses-Lorente, G., Bech, N., White, A. M., & Parr, G. (2010). Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin: no clinically relevant drug-drug interactions. Journal of Clinical Pharmacology, 50(10), 1188-201. https://doi.org/10.1177/0091270009358709
Derks M, et al. Coadministration of Dalcetrapib With Pravastatin, Rosuvastatin, or Simvastatin: No Clinically Relevant Drug-drug Interactions. J Clin Pharmacol. 2010;50(10):1188-201. PubMed PMID: 20489031.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin: no clinically relevant drug-drug interactions. AU - Derks,Michael, AU - Abt,Markus, AU - Phelan,Mary, AU - Turnbull,Lynn, AU - Meneses-Lorente,Georgina, AU - Bech,Nuria, AU - White,Anne-Marie, AU - Parr,Graeme, Y1 - 2010/05/20/ PY - 2010/5/22/entrez PY - 2010/5/22/pubmed PY - 2011/1/8/medline SP - 1188 EP - 201 JF - Journal of clinical pharmacology JO - J Clin Pharmacol VL - 50 IS - 10 N2 - Dalcetrapib targets cholesteryl ester transfer protein and increases high-density lipoprotein cholesterol (HDL-C) levels. It is in clinical development for the prevention of cardiovascular events and will likely be used in combination with standard of care, including statins. Three crossover studies in healthy males investigated the pharmacokinetic drug-drug interaction potential of 900 mg dalcetrapib and statins: two 3-period studies (dalcetrapib plus pravastatin or rosuvastatin) and a 2-period study (dalcetrapib plus simvastatin). Effect on lipids and safety were secondary end points. The 900 mg dose investigated is higher than the 600 mg dose currently being investigated in Phase III. Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin was not associated with significant increases in statin exposure except for a 26% increase in rosuvastatin C(max) (90% CI 1.088 to 1.468) but not AUC(0-24) (90% CI 0.931 to 1.085). Dalcetrapib AUC(0-24) and C(max) were not significantly altered by coadministration with pravastatin, and were significantly lower when dalcetrapib was coadministered with rosuvastatin or simvastatin compared with dalcetrapib alone. The HDL-C increase with dalcetrapib was not compromised by coadministration with statins, and reduction in low-density lipoprotein cholesterol with dalcetrapib coadministered with statins was greater than with statins alone. Dalcetrapib alone and coadministered with statins was generally well tolerated. SN - 1552-4604 UR - https://www.unboundmedicine.com/medline/citation/20489031/Coadministration_of_dalcetrapib_with_pravastatin_rosuvastatin_or_simvastatin:_no_clinically_relevant_drug_drug_interactions_ L2 - https://doi.org/10.1177/0091270009358709 DB - PRIME DP - Unbound Medicine ER -