Potential benefit of vitamin D supplementation in people with respiratory illnesses, during the COVID-19 pandemic.

This review describes the evidence for the potential benefit of vitamin D supplementation in people with respiratory diseases who may have a higher susceptibility to coronavirus disease 2019 (COVID-19) infection and its consequences. Clinical evidence indicates that vitamin D may reduce the risk of both upper and lower respiratory tract infections and offers benefit particularly in people with vitamin D deficiency. Some evidence exists for a higher incidence of active tuberculosis (TB) in patients who are deficient in vitamin D. An association between low levels of 25(OH)D (the active form of vitamin D) and COVID-19 severity of illness and mortality has also been reported. In addition, low 25(OH)D levels are associated with poor outcomes in acute respiratory distress syndrome (ARDS). The cytokine storm experienced in severe COVID-19 infections results from excessive release of pro-inflammatory cytokines. Due to its immunomodulatory effects, adequate vitamin D levels may cause a decrease in the pro-inflammatory cytokines and an increase in the anti-inflammatory cytokines during COVID-19 infections. Vitamin D deficiency was found in 82.2% of hospitalized COVID-19 cases and 47.2% of population-based controls (p < 0.0001). The available evidence warrants an evaluation of vitamin D supplementation in susceptible populations with respiratory diseases, such as TB, and particularly in those who are deficient in vitamin D. This may mitigate against serious complications of COVID-19 infections or reduce the impact of ARDS in those who have been infected.

Impact of CYP polymorphisms, ethnicity and sex differences in metabolism on dosing strategies: the case of efavirenz.

PURPOSE: Differences in drug metabolism due to cytochrome P450 (CYP) polymorphisms may be significant enough to warrant different dosing strategies in carriers of specific cytochrome P450 (CYP) polymorphisms, especially for drugs with a narrow therapeutic index. The impact of such polymorphisms on drug plasma concentrations and the resulting dosing strategies are presented in this review, using the example of efavirenz (EFV). METHODS: A structured literature search was performed to extract information pertaining to EFV metabolism and the influence of polymorphisms of CYP2B6, ethnicity, sex and drug interactions on plasma concentrations of EFV. The corresponding dosing strategies developed for carriers of specific CYP2B6 genotypes were also reviewed. RESULTS: The polymorphic CYP2B6 enzyme, which is the major enzyme in the EFV metabolic pathway, is a key determinant for the significant inter-individual differences seen in EFV pharmacokinetics and pharmacodynamics (PKPD). Ethnic differences and the associated prevalence of CYP2B6 polymorphisms result in significant differences in the PKPD associated with a standard 600 mg per day dose of EFV, warranting dosage reduction in carriers of specific CYP2B6 polymorphisms. Drug interactions and auto-induction also influence EFV PKPD significantly. CONCLUSION: Using EFV as an example of a drug with a narrow therapeutic index and a high inter-patient variability in plasma concentrations corresponding to a standard dose of the drug, this review demonstrates how genotyping of the primary metabolising enzyme can be useful for appropriate dosage adjustments in individuals. However, other variables such as drug interactions and auto-induction may necessitate plasma concentration measurements as well, prior to personalising the dose.