Fig. 1 shows the chemical structures of hydroxychloroquine and azithromycin. Although the two compounds are from two chemically distinct classes, they have a structural similarity that is pharmacokinetically relevant. Both compounds are multibasic amines with pKa values that are susceptible to protonation in the physiological pH range. Azithromycin has two nitrogens with pKa values of 8.1 and 8.8 [5]. Hydroxychloroquine has three nitrogens with pKa values of 4.0, 8.3 and 9.7 [6]. However, only the two nitrogens with the higher values (shown in circles in Fig. 1) are protonated under physiological conditions.
Fig. 1 Chemical structures of hydroxychloroquine and azithromycin. The circles indicate the pH-sensitive basic nitrogens.