Favipiravir inhibits acetaminophen sulfate formation but minimally affects systemic pharmacokinetics of acetaminophen.

AIMS: The antiviral agent favipiravir is likely to be co-prescribed with acetaminophen (paracetamol). The present study evaluated the possiblility of a pharmacokinetic interaction between favipiravir and acetaminophen, in vitro and in vivo. METHODS: The effect of favipivir on the transformation of acetaminophen to its glucuronide and sulfate metabolites was studied using a pooled human hepatic S9 fraction in vitro. The effect of acute and extended adminstration of favipiravir on the pharmacokinetics of acetaminophen and metabolites was evaluated in human volunteers. RESULTS: Favipiravir inhibited the in vitro formation of acetaminophen sulfate, but not acetaminophen glucuronide. In human volunteers, both acute (1 day) and extended (6 days) administration of favipiravir slightly but significantly increased (by about 20 %) systemic exposure to acetaminophen (total AUC), whereas Cmax was not significantly changed. AUC for acetaminophen glucuronide was increased by 23 to 35 % above control by favipiravir, while AUC for acetaminophen sulfate was reduced by about 20 % compared to control. Urinary excretion of acetaminophen sulfate was likewise reduced to 44 to 65 % of control values during favipiravir co-administration, while excretion of acetaminophen glucuronide increased to 17 to 32 % above control. CONCLUSION: Favipiravir inhibits acetaminophen sulfate formation in vitro and in vivo. However the increase in systemic exposure to acetaminophen due to favipiravir co-administration, though statistically significant, is small in magnitude and unlikely to be of clinical importance.

Enhancement and suppression of vibrational coherence in degenerate four-wave-mixing signal generated from dye-doped polymer films.

Vibrational coherence in the degenerate four-wave-mixing (DFWM) signal generated from polymer films doped with a dye, oxazine 4 (Ox4), at 10 K was investigated. It was found that the amplitudes of some low-frequency oscillations (<400 cm(-1)) were enhanced when the delay between the first and second femtosecond pulses was set out of phase with the oscillation period. Frequency and reorganization energy dependence was investigated by computer simulation based on the response function formalism which considers all the possible Liouville space pathways for the DFWM signal. It was revealed that low-frequency oscillations with weak coupling to the optical transition can be enhanced in the stimulated photon echo signal compared to the transient grating signal.