Gemfibrozil concentrations are significantly decreased in the presence of lopinavir-ritonavir.
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).


CONCLUSIONS
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.
Busse
Kristin H
KH
Clinical Pharmacokinetics Research Laboratory, Pharmacy Department, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Hadigan
Colleen
C
Chairez
Cheryl
C
Alfaro
Raul M
RM
Formentini
Elizabeth
E
Kovacs
Joseph A
JA
Penzak
Scott R
SR
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D004336:Drug Antagonism; D005260:Female; D015248:Gemfibrozil / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011744:Pyrimidinones / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage*
D019380:Anti-HIV Agents; D000960:Hypolipidemic Agents; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir; D015248:Gemfibrozil