Background: Hydroxychloroquine (HCQ) is an inhibitor of COVID-19, demonstrated by in-vitro data. There is no pharmacokinetic data on HCQ for pre-exposure prophylaxis in Indians. We estimated the peak and trough blood levels achieved on prophylactic dose HCQ administration.
Methods: We conducted an observational study from July to October 2020 at St. John’s Medical College and Research Institute, Bengaluru, India. 24 asymptomatic healthcare workers taking HCQ prophylaxis for COVID-19 infection, as advised by their treating physicians were included. The pre-dose (0.00 hour) blood sample (2 mL each) was collected prior to dosing on day 1 (morning dose) and prior to each weekly dose for the next seven weeks. The post-dose samples (2 mL each) were collected 4.00 hours after the first dose on day 1 and also on 3rd (340 h) and 5th week (676 h). Altogether 11 blood samples were collected from each volunteer. HCQ in blood was determined using a validated LCMS/MS method. Amodiaquine was used as internal standard. The minimum HCQ trough concentration to inhibit 50% of viral infection (EC50) is 0.72μM.
Results: Mean pre dose trough concentration (± SD) in ug/mL on day 7, 14, 21, 28 and 35 was 0.0554 (0.0406); 0.0770 (0.0340); 0.0835 (0.0368); 0.0869 (0.0372) and 0.1072 (0.0639) respectively. A gradual increase in trough concentration of HCQ was noticed till day 35. This concentration remained the same on day 42 and day 49. HCQ was tolerated well by the volunteers and all of them completed the study without being reported as COVID-19 positive.
Conclusion: In our study, HCQ at the 800 mg loading dose followed by 400 mg once a week did not attain the minimum HCQ trough concentration required to inhibit 50% of viral infection (EC50).
