Investigating the interaction between nifedipine- and ritonavir-containing antiviral regimens: A physiologically based pharmacokinetic/pharmacodynamic analysis.

AIMS: Hypertension is a common comorbidity of patients with COVID-19, SARS or HIV infection. Such patients are often concomitantly treated with antiviral and antihypertensive agents, including ritonavir and nifedipine. Since ritonavir is a strong inhibitor of CYP3A and nifedipine is mainly metabolized via CYP3A, the combination of ritonavir and nifedipine can potentially cause drug-drug interactions. This study provides guidance on nifedipine treatment during and after coadministration with ritonavir-containing regimens, using a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) analysis. METHODS: The PBPK/PD models for 3 formations of nifedipine were developed based on the Simcyp nifedipine model and the models were verified using published data. The effects of ritonavir on nifedipine exposure and systolic blood pressure (SBP) were assessed for instant-release, sustained-release and controlled-release formulations in patients. Various nifedipine regimens were investigated when coadministered with or without ritonavir. RESULTS: PBPK/PD models for 3 formulations of nifedipine were successfully established. The predicted maximum concentration (Cmax ), area under plasma concentration-time curve (AUC), maximum reduction in SBP and area under effect-time curve were all within 0.5-2.0-fold of the observed data. Model simulations showed that the inhibitory effect of ritonavir on CYP3A4 increased the Cmax of nifedipine 17.92-48.85-fold and the AUC 63.30-84.01-fold at steady state and decreased the SBP by >40 mmHg. Thus, the combination of nifedipine and ritonavir could lead to severe hypotension. CONCLUSION: Ritonavir significantly affects the pharmacokinetics and antihypertensive effect of nifedipine. It is not recommended for patients to take nifedipine- and ritonavir-containing regimens simultaneously.

Medication therapy strategies for the coronavirus disease 2019 (COVID-19): recent progress and challenges.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has spread globally since it outbroke in December 2019. The urgent pandemic presents an unprecedented challenge to develop and identify effective medication therapy strategies to combat the COVID-19. AREAS COVERED: Here, we summarized and evaluated the current treatment drugs and regimens, and put forward the treatment recommendations, including using the potential repurposed or experimental drugs against COVID-19, e.g. chloroquine (CQ), hydroxychloroquine (HCQ), lopinavir/ritonavir (LPV/r), remdesivir (RDV), and favipiravir (FPV). We also analyzed the specific drugs and vaccines against SARS-CoV-2 ongoing development and formulated the comprehensive treatment regimens based on condition of patients, diseases and drugs as well as concomitant medications. EXPERT OPINION: No drugs and vaccines have been proven to be particularly effective against SARS-CoV-2 up to now. The recommended comprehensive medication therapy strategies have already displayed favorable effect in the fight against COVID-19. Research should be focused on the development of anti-SARS-CoV-2 drugs and vaccines based on high-quality clinical trial evidence, treatment guidelines and expert consensus.