Tecovirimat concentrations and viral suppression in seminal fluid from patients with mpox

With the aim of investigating the penetration of tecovirimat into seminal fluid, plasma and semen were obtained from three individuals admitted to hospital with severe mpox and treated with the standard dose of oral tecovirimat (600 mg twice daily) for 14 days.1 Tecovirimat concentrations were measu...

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Bibliographic Details
Published in:The Lancet infectious diseases 2023-05, Vol.23 (5), p.531-532
Main Authors: Tempestilli, Massimo, Mondi, Annalisa, Matusali, Giulia, Mariotti, Davide, Pinnetti, Carmela, Beccacece, Alessia, Cimini, Eleonora, Mazzotta, Valentina, Carletti, Fabrizio, Faccendini, Paolo, Maggi, Fabrizio, Girardi, Enrico, Nicastri, Emanuele, Vaia, Francesco, Antinori, Andrea
Format: Article
Language:English
Subjects:
Active transport
Deoxyribonucleic acid
Disease resistance
DNA
DNA viruses
Efflux
Fetus
Humans
Infectious diseases
Liquid chromatography
Mass spectrometry
Mass spectroscopy
Mpox
Mpox (monkeypox)
Patients
Pharmacokinetics
Plasma
Sanctuaries
Semen
Seminal fluid
Substrates
Viruses
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Summary:With the aim of investigating the penetration of tecovirimat into seminal fluid, plasma and semen were obtained from three individuals admitted to hospital with severe mpox and treated with the standard dose of oral tecovirimat (600 mg twice daily) for 14 days.1 Tecovirimat concentrations were measured using a modified and validated liquid chromatography with a tandem mass spectrometry method.2 Additionally, in the same individuals, the monkeypox virus DNA (MPXV-DNA) load in the seminal fluid was evaluated at baseline, during, and after tecovirimat treatment, using real-time PCR. [...]the drug is not a substrate for efflux transporters.1 We can speculate that tecovirimat could be distributed into the seminal fluid through passive diffusion of unbound drug fraction and that active transport of tecovirimat out of this compartment should be minimal. In all our patients, we observed sustained clearance of MPXV-DNA from semen samples approximately after the first week of treatment, according to tecovirimat pharmacokinetics steady-state levels.1 Although spontaneous viral clearance is a probable hypothesis considering the baseline low viral loads of our patients and the viral kinetics previously described in this compartment for untreated patients,4–5 the drug concentrations found in semen might be relevant in terms of transmission, potential antiviral resistance, and potential viral sanctuaries (eg, lingering virus observed in monkeys).6 We declare no competing interests.
ISSN:1473-3099
1474-4457
DOI:10.1016/S1473-3099(23)00214-1