The protease inhibitors ritonavir and saquinavir influence lipid metabolism: a pig model for the rapid evaluation of new drugs.
BACKGROUND
Studies of the effects of antiretroviral drugs on lipid metabolism are limited by the availability of suitable models. We have thus developed an animal model utilising Göttingen mini-pigs. The normal lipid metabolism of mini-pigs closely reflects that of humans and they are expected to have similar reactions to antiretroviral drugs.


METHODS
The pigs were treated orally with high doses of the protease inhibitors ritonavir and saquinavir for 4 weeks. The model allows repeated concomitant biopsies from liver, muscle, adipose tissue and plasma samples.


RESULTS
The study showed a general decrease in polyunsaturated fatty acids; changes in both saturated and monounsaturated fatty acids were also apparent after antiretroviral treatment. The changes were observed after 4 weeks of treatment. At 4 weeks post-treatment, the levels of all fatty acids were lower compared with pretreatment levels, suggesting a prolonged effect of the antiretroviral drug treatment lasting beyond the 4 week post-treatment observation period.


CONCLUSIONS
The Göttingen mini-pig model is a promising animal model for rapid screening of the metabolic effects induced by antiretroviral drugs.
Petersen
Eskild
E
Department of Infectious Diseases, Aarhus University Hospital, Skejby, Aarhus, Denmark. joepeter@rm.dk
Mu
Huiling
H
Porsgaard
Trine
T
Bertelsen
Lone S
LS
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology; D004334:Drug Administration Schedule; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D023421:Models, Animal; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology; D019258:Saquinavir / Q000008:administration & dosage / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors
D019380:Anti-HIV Agents; D005227:Fatty Acids; D019258:Saquinavir; D019438:Ritonavir