Plasma levels of hydroxychloroquine and seroconversion in health care workers during COVID prophylaxis: Retrospective evaluation using pharmacokinetic simulation

Abstract

Objectives: Hydroxychloroquine (HCQ) was repurposed for prophylactic use against coronavirus disease-19. However, justification for the different regimens used for prophylaxis lacks rationale. Thus, this study retrospectively assessed the therapeutic plasma levels of HCQ using simulation-based pharmacokinetic estimates for rationalising the dose of HCQ. Materials and Methods: A total of 246 healthcare workers (HCWs) took the HCQ prophylaxis as per the Indian Council of Medical Research (ICMR) dosing. Besides, healthy volunteers (HWs) consumed HCQ following the ICMR regimen. Serum levels of HCQ in HCWs and HWs were analysed using liquid chromatography tandem mass spectrometry (LC-MS/MS). The detected HCQ levels pharmacokinetic parameters were derived and used for the simulation studies to predict free drug and lung (tissue) levels. The HCQ levels were correlated with seroconversion, and adverse effects and correlated with predicted levels. Results: The HCQ plasma concentration of HCWs falls into the therapeutic window of HCQ as predicted by the simulation studies. The simulated data showed that the ratio of plasma to lung (tissue levels) as well as to epithelial lining fluid levels (free drug levels) could reach in adequate levels of reported IC50. Poor correlation was observed for the HCQ concentration and duration of prophylactic treatment in HCWs, while the seropositivity was negatively correlated with the HCQ levels in non-responders in HCWs. Conclusion: The study revealed that adequate plasma HCQ levels were reached following the prophylaxis schedule to exhibit protection against severe acute respiratory syndrome coronavirus 2. However, the lack of any advantages in the clinical studies highlights the paradox of the absence of in vitro-in vivo correlation.