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Clin Drug Investig. 2014 Jul;34(7):475-82. doi: 10.1007/s40261-014-0198-x.

Steady-state pharmacokinetics of darunavir/ritonavir and pitavastatin when co-administered to healthy adult volunteers.

Author information

1
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, DC 0545, Indianapolis, IN, 46285, USA, yucy@lilly.com.

Abstract

BACKGROUND:

The treatment of hyperlipidaemia in human immunodeficiency virus (HIV)-infected patients has become increasingly important. However, treatment options are limited because of the drug-drug interaction between certain statins and HIV medications metabolized by cytochrome P450 (CYP) enzymes.

OBJECTIVES:

The primary objective was to investigate the steady-state pharmacokinetics of pitavastatin when co-administered with darunavir/ritonavir. The secondary objective was to investigate the steady-state pharmacokinetics of both darunavir and ritonavir when co-administered with pitavastatin.

METHODS:

This was a single-centre, open-label, multi-dose, fixed-sequence study in HIV seronegative healthy volunteers. Pitavastatin 4 mg was administered once daily on days 1-5 and on days 12-16, and darunavir 800 mg/ritonavir 100 mg once daily on days 6-16. Pharmacokinetic blood sampling was performed on days 5, 11 and 16. No significant interaction was concluded if the 90 % confidence intervals (CIs) of the geometric mean ratios (GMRs) for total exposure [i.e. the area under the plasma concentration-time curve over a dosing interval at steady state (AUC(0-τ))] and for peak exposure [i.e. the maximum plasma concentration (C(max))] of the two treatments were within the 80-125 % range.

RESULTS:

Twenty-eight subjects (mean age 30.5 years) were enrolled, and pharmacokinetic data were available for 27 subjects. For pitavastatin, the GMRs and 90 % CIs for the AUC(0-τ) and C(max) ratios with co-administration were 0.74 (0.69-0.80) and 0.96 (0.84-1.09), respectively. For both darunavir and ritonavir, the 90 % CIs for the AUC(0-τ) and C max ratios were within 80-125 % with pitavastatin co-administration. No significant safety issues were reported.

CONCLUSION:

Darunavir/ritonavir decreased total exposure to pitavastatin by 26 %, while peak exposures were similar. Pitavastatin did not influence the pharmacokinetics of darunavir or ritonavir. There is limited interaction between pitavastatin and darunavir/ritonavir.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01422369.

PMID:
24825411
DOI:
10.1007/s40261-014-0198-x
[Indexed for MEDLINE]

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