Spectroscopic studies involving antiretrovirals
Drug-drug interaction issues continue to present a major dilemma for the clinician caring for complex patients such as those infected with HIV and malaria. Although the consequences of co-infection with HIV and malaria parasites are not fully understood, available evidence suggests that the infections act synergistically and together result in worse outcomes. Controlled interaction studies are often not available and are needed. This study has examined the in vitro interactions between agents commonly prescribed for patients with HIV and malaria in the presence of metal ions using spectroscopic techniques. The structures of all the antiretroviral and antimalarial drugs, except Lopinavir and hydroxychloroquine, were found to be affected by a change in pH. UV-Visible spectra detected the interactions between antiretroviral and antimalarial drugs. In most cases, the increase of antimalarial drug to that of antiretroviral drug showed increased interaction. Acyclovir interacted strongly with all three antimalarial drugs. Efavirenz and lopinavir interacted with the three all antimalarial drugs, but not as intensely as acyclovir. Metal ions were shown to modify the structure of all antiretroviral drugs. In each case, antiretroviral drug in the presence of each metal ion increased the intensity of the antiretroviral. This indicates that the interaction of antiretroviral and metal ions causes a synergistic effect on the complex, reducing their solubility and also their bioavailability. The interaction between quinine and the three antiretroviral is amplified in the presence of Mg. Fluorescence spectra showed that the antiretroviral are transformed into different species when they interact with antimalarial and metal ions. Infrared spectra showed that antiretrovirals use the N atom of their amine, or amide group or O atom of their CO group to interact with antimalarial drugs. NMR spectra show that primaquine interacts most with each antiretroviral drug, especially efavirenz. These studies are needed to initiate in vivo controlled interaction studies between antiretroviral and antimalarial drugs.
Courtney A Kennemore,
"Spectroscopic studies involving antiretrovirals"
ETD Collection for Tennessee State University.