Pharmacokinetics of tecovirimat in subjects with Mpox

Objective: To investigate the pharmacokinetics (PK) of tecovirimat in subjects with Mpox. Methods: This monocentric, prospective, observational study enrolled subjects with Mpox who received standard treatment with oral tecovirimat. Plasma samples for PK assessment were collected at steady state (5-8 days after initiation of antiviral therapy), before and 3, 5, 7 and 12 h after tecovirimat administration. Drug concentrations were determined by validated liquid chromatography coupled with tandem mass spectrometry. PK parameters were calculated using Phoenix 8.1. Results: Overall, 14 male patients hospitalized for severe Mpox with ongoing tecovirimat treatment were enrolled in this study. Six of the 14 patients were living with human immunodeficiency virus (HIV), all of whom were on antiretroviral therapy (ART) and virologically suppressed at the time of hospitalization. Significant differences in tecovirimat PK were observed in subjects without HIV compared with subjects with HIV. In subjects with HIV, the maximum tecovirimat plasma concentration (39%, P <= 0.0 0 01), minimum tecovirimat plasma concentration (42%, P = 0.0079) and area under the curve from zero to the last measured time -point (40%, P <= 0.0 0 01) were significantly lower compared with subjects without HIV, but all concentrations remained above the in -vitro calculated 90% inhibitory concentration. No significant associations were found between demographic/clinical data and tecovirimat PK. All patients recovered completely within 14 (range 6-36) days of treatment initiation. Conclusions: This study found a significant decrease in plasma exposure of tecovirimat in Mpox patients with HIV on effective ART compared with those without HIV, with no evident impact on clinical outcomes. Although these results need to be confirmed in larger studies, they may provide useful information on the PK of tecovirimat. (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )