Abstract
The concept of pharmacokinetic enhancement can be traced back to the 1940s when probenecid was added to extend penicillin exposure. It revived in the 1990s with the advent of HIV combined antiretroviral therapies, when ritonavir was shown to markedly increase the circulating concentrations of saquinavir and other HIV protease inhibitors. Along with cobicistat, ritonavir remains widely used as a booster to leverage the effectiveness of co-administered antiretrovirals: both substances are potent cytochrome P450 inhibitors that reduce metabolic activity, extend drug half-lives, and improve the bioavailability of a wide range of concomitant drugs at sustained plasma concentrations.
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