Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers.
BACKGROUND
Some HIV protease inhibitors (PIs) have been shown to induce insulin resistance in vitro but the degree to which specific PIs affect insulin sensitivity in humans is less well understood.


METHODS
In two separate double-blind, randomized, cross-over studies, we assessed the effects of a single dose of ritonavir (800 mg) and amprenavir (1200 mg) on insulin sensitivity (euglycemic hyperglycemic clamp) in healthy normal volunteers.


RESULTS
Ritonavir decreased insulin sensitivity (-15%; P = 0.008 versus placebo) and non-oxidative glucose disposal (-30%; P = 0.0004), whereas neither were affected by amprenavir administration.


CONCLUSIONS
Compared to previously performed studies of identical design using single doses of indinavir and lopinavir/ritonavir, a hierarchy of insulin resistance was observed with the greatest effect seen with indinavir followed by ritonavir and lopinavir/ritonavir, with little effect of amprenavir.
Lee
Grace A
GA
Department of Medicine, University of California, San Francisco, California, USA. grace.lee.2@ucsf.edu
Rao
Madhu
M
Mulligan
Kathleen
K
Lo
Joan C
JC
Aweeka
Francesca
F
Schwarz
Jean-Marc
JM
Schambelan
Morris
M
Grunfeld
Carl
C
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology*; D004311:Double-Blind Method; D004734:Energy Metabolism; D005663:Furans; D015309:Glucose Clamp Technique; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D019469:Indinavir / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007333:Insulin Resistance; D019344:Lactic Acid / Q000097:blood; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000494:pharmacology; D019438:Ritonavir / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
D001786:Blood Glucose; D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D007328:Insulin; D011744:Pyrimidinones; D013449:Sulfonamides; D061466:Lopinavir; D019344:Lactic Acid; C095108:amprenavir; D019469:Indinavir; D019438:Ritonavir