Gemfibrozil concentrations are significantly decreased in the presence of lopinavir-ritonavir. J Acquir Immune Defic Syndr 2009 Oct 01;52(2):235-9
Date
08/04/2009Pubmed ID
19648824Pubmed Central ID
PMC2815103DOI
10.1097/QAI.0b013e3181b0610eScopus ID
2-s2.0-70349680871 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
OBJECTIVE: The objective of this study was to determine the influence of a 2-week course of lopinavir-ritonavir on the pharmacokinetics of the triglyceride-lowering agent, gemfibrozil.
METHODS: The study was conducted as an open label, single-sequence pharmacokinetic study in healthy human volunteers. Gemfibrozil pharmacokinetic parameter values were compared using a Student t test after a single 600-mg dose was administered to healthy volunteers before and after 2 weeks of lopinavir-ritonavir (400/100 mg) twice daily.
RESULTS: Fifteen healthy volunteers (eight males) completed the study. All study drugs were generally well tolerated and no subjects withdrew participation. The geometric mean ratio (90% confidence interval) for gemfibrozil area under the plasma concentration-time curve after 14 days of lopinavir-ritonavir compared with baseline was 0.59 (0.52, 0.67) (P < 0.001). All 15 study subjects experienced a reduction in gemfibrozil area under the plasma concentration-time curve after lopinavir-ritonavir (range, -6% to -74%). The geometric mean ratios for gemfibrozil apparent oral clearance and maximum concentration were 1.69 (1.41, 1.97) and 0.67 (0.49, 0.86) after 14 days of lopinavir-ritonavir versus baseline, respectively (P < 0.0001 and 0.01, respectively). Gemfibrozil elimination half-life did not change after lopinavir-ritonavir administration (P = 0.60).
CONCLUSION: Lopinavir-ritonavir significantly reduced the systemic exposure of gemfibrozil by reducing gemfibrozil absorption. Clinicians treating HIV-infected patients with hypertriglyceridemia should be aware of this drug interaction.
Author List
Busse KH, Hadigan C, Chairez C, Alfaro RM, Formentini E, Kovacs JA, Penzak SRAuthor
Kristin Busse PharmD Assistant Professor in the School of Pharmacy Administration department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAnti-HIV Agents
Drug Antagonism
Female
Gemfibrozil
Healthy Volunteers
Humans
Hypolipidemic Agents
Lopinavir
Male
Middle Aged
Plasma
Pyrimidinones
Ritonavir
