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Pharmacokinetic considerations to optimize clinical outcomes for COVID-19 drugs

ABSTRACT: The development of clinically effective drugs that could complement existing vaccines is urgently needed to reduce the morbidity and mortality associated with COVID-19. Drug-metabolizing enzymes, membrane-associated drug transporters, and inflammatory responses can partly determine the safety and efficacy of COVID-19 drugs by controlling their concentrations in both the systemic circulation and in peripheral tissues. It is still unknown how these factors affect how well COVID-19 drugs work in the clinic. We explore how drug metabolism and transport, as well as SARS-CoV-2-associated inflammatory response at disease target sites, may affect the clinical outcomes of COVID-19 drugs. In addition, we provide expert opinion on potential strategies for overcoming the clinical pharmacology and pathophysiological obstacles to improve COVID-19 drug effectiveness.

SUBMITTER: Nwabufo C

PROVIDER: S-EPMC9510059 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Project description:AimsThe aim of this study was to continually evaluate the association between cardiovascular drug exposure and COVID-19 clinical outcomes (susceptibility to infection, disease severity, hospitalization, hospitalization length, and all-cause mortality) in patients at risk of/with confirmed COVID-19.MethodsEligible publications were identified from more than 500 databases on 1 November 2020. One reviewer extracted data with 20% of the records independently extracted/evaluated by a second reviewer.ResultsOf 52 735 screened records, 429 and 390 studies were included in the qualitative and quantitative syntheses, respectively. The most-reported drugs were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) with ACEI/ARB exposure having borderline association with confirmed COVID-19 infection (OR 1.14, 95% CI 1.00-1.31). Among COVID-19 patients, unadjusted estimates showed that ACEI/ARB exposure was associated with hospitalization (OR 1.76, 95% CI 1.34-2.32), disease severity (OR 1.40, 95% CI 1.26-1.55) and all-cause mortality (OR 1.22, 95% CI 1.12-1.33) but not hospitalization length (mean difference -0.27, 95% CI -1.36-0.82 days). After adjustment, ACEI/ARB exposure was not associated with confirmed COVID-19 infection (OR 0.92, 95% CI 0.71-1.19), hospitalization (OR 0.93, 95% CI 0.70-1.24), disease severity (OR 1.05, 95% CI 0.81-1.38) or all-cause mortality (OR 0.84, 95% CI 0.70-1.00). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with confirmed COVID-19 infection (OR 0.93, 95% CI 0.79-1.09), hospitalization (OR 0.84, 95% CI 0.58-1.22), hospitalization length (mean difference -0.14, 95% CI -1.65-1.36 days), disease severity (OR 0.92, 95% CI 0.76-1.11) while it decreased the odds of dying (OR 0.76, 95% CI 0.65-0.88). A similar trend was observed for other cardiovascular drugs. However, the validity of these findings is limited by a high level of heterogeneity and serious risk of bias.ConclusionCardiovascular drugs are not associated with poor COVID-19 outcomes in adjusted analyses. Patients should continue taking these drugs as prescribed.

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Pharmacokinetic considerations to optimize clinical outcomes for COVID-19 drugs

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