Introduction: Drug-drug interactions can occur on every pharmacokinetic level, including absorption, distribution, metabolism (biotransformation) and excretion. The most common and most studied drug-drug interactions occur at the level of biotransformation, where the cytochrome P450 family plays the major role. In most cases, inhibition of CYP enzymes by one drug, can lead to increased serum levels of other simultaneously administered drugs and to a greater potential for toxicity. In the pharmacokinetic boosting concept there is a benefit of such drug-drug interaction, where alterations in metabolic rates of one pharmaceutical agent through the inhibitory effects of another agent lead to increases in plasma concentrations and prolongation of the half-life of the co-administered agent.
Materials and Methods: For the purposes of this review, we have studied two literature databases (Pubmed and Science direct). Keywords used in the search were: `ritonavir`, `cobicistat`, ` pharmacokinetic `, and `boosting`.
Results: This boosting concept is widely used in the treatment of HIV infections. The most studied drugs are ritonavir (initially developed as an HIV PI, but it is currently used primarily as a PK boosting agent) and cobicistat. Ritonavir is a very potent CYP3A4 inhibitor, also able to inhibit or induce other CYP subfamilies, which is responsible for a large number of drug-drug interactions. Cobicistat, was approved in 2012. Its unique pharmacological property is the selective inhibition of CYP3A. Both drugs, ritonavir 100 mg and cobicistat 150 mg, nowadays are used as a combined ART-boosting agents together with a second-generation PI, i.e., atazanavir or darunavir. In 2015, the first boosted protease inhibitor in fixed dose combination - Rezolsta®(darunavir/cobicistat) was approved.
Conclusion: Pharmacokinetic boosting is a very promising concept. It can be used on the one hand to reduce the dose of the boosted drug and on the other - to increase compliance and to improve adherence.
