Pharmacokinetics and pharmacodynamics of cytochrome P450 inhibitors for HIV treatment

• Published in: Expert opinion on drug metabolism & toxicology Vol. 15; no. 5; p. 417
• Main Authors: Gong, Yuqing, Haque, Sanjana, Chowdhury, Pallabita, Cory, Theodore J, Kodidela, Sunitha, Yallapu, Murali M, Norwood, John M, Kumar, Santosh
• Format: Journal Article
• Language: English
• Published: England 04.05.2019
• Subjects: Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - pharmacology; Cytochrome P-450 Enzyme Inhibitors - administration & dosage; Cytochrome P-450 Enzyme Inhibitors - pharmacokinetics; Cytochrome P-450 Enzyme Inhibitors - pharmacology; Cytochrome P-450 Enzyme System - drug effects; Cytochrome P-450 Enzyme System - genetics; Drug Interactions; HIV Infections - drug therapy; Humans; nanoparticles; CYP inhibitors; HIV; pharmacodynamics; Antiretroviral therapy; drug–drug interactions
• ISSN: 1744-7607
• DOI: 10.1080/17425255.2019.1604685

Drugs used in HIV treatment; all protease inhibitors, some non-nucleoside reverse transcriptase inhibitors, and pharmacoenhancers ritonavir and cobicistat can inhibit cytochrome P450 (CYP) enzymes. CYP inhibition can cause clinically significant drug-drug interactions (DDI), leading to increased drug exposure and potential toxicity. Areas covered: A complete understanding of pharmacodynamics and CYP-mediated DDI is crucial to prevent adverse side effects and to achieve optimal efficacy. We summarized the pharmacodynamics of all the CYP inhibitors used for HIV treatment, followed by a discussion of drug interactions between these CYP inhibitors and other drugs, and a discussion on the effect of CYP polymorphisms. We also discussed the potential advancements in improving the pharmacodynamics of these CYP inhibitors by using nanotechnology strategy. Expert opinion: The drug-interactions in HIV patients receiving ARV drugs are complicated, especially when patients are on CYP inhibitors-based ART regimens. Therefore, evaluation of CYP-mediated drug interactions is necessary prior to prescribing ARV drugs to HIV subjects. To improve the treatment efficacy and minimize DDI, novel approaches such as nanotechnology may be the potential alternative approach. However, further studies with large cohort need to be conducted to provide strong evidence for the use of nano-formulated ARVs to effectively treat HIV patients.