Lopinavir-ritonavir: effects on endothelial cell function in healthy subjects.
To differentiate between the effects that antiretroviral drugs have on the endothelium and the secondary effects that they have on immune function, viral load, and dyslipidemia, 6 non-human immunodeficiency virus-infected human subjects were treated with lopinavir-ritonavir for 1 month and, on the basis of forearm blood flow, the treatment's effects on endothelial cell function were measured. Surprisingly, after exposure to lopinavir-ritonavir, absolute forearm blood-flow responses to the endothelium-dependent vasodilator, acetylcholine, increased significantly (P=.03), and forearm blood flow decreased to a greater extent during specific inhibition of NO synthase by N(G)-monomethyl-L-arginine. Thus, in this small cohort of subjects, short-term treatment with lopinavir-ritonavir does not appear to directly promote endothelial cell dysfunction.
Grubb
Jessica R
JR
Critical Care Medical Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
Dejam
André
A
Voell
Jocelyn
J
Blackwelder
William C
WC
Sklar
Peter A
PA
Kovacs
Joseph A
JA
Cannon
Richard O
RO
Masur
Henry
H
Gladwin
Mark T
MT
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects*; D012039:Regional Blood Flow; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
D004791:Enzyme Inhibitors; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019323:omega-N-Methylarginine; D000109:Acetylcholine; D019438:Ritonavir