title: Favipiravir inhibits acetaminophen sulfate formation but minimally affects systemic pharmacokinetics of acetaminophen.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA.
authors: Yanli
authors: Y
authors: Zhao
authors: Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA.
authors: Jerold S
authors: JS
authors: Harmatz
authors: MediVector, Inc., Cambridge, MA, USA.
authors: Carol R
authors: CR
authors: Epstein
authors: Drug Safety, Metabolism & Pharmacokinetics Department, Research Laboratories, Toyama Chemical Co., LTD, Tokyo, Japan.
authors: Yukako
authors: Y
authors: Nakagawa
authors: Drug Safety, Metabolism & Pharmacokinetics Department, Research Laboratories, Toyama Chemical Co., LTD, Tokyo, Japan.
authors: Chie
authors: C
authors: Kurosaki
authors: Clinical Research Department, Clinical Pharmacology Group, Toyama Chemical Co., LTD, Tokyo, Japan.
authors: Tetsuro
authors: T
authors: Nakamura
authors: Drug Safety, Metabolism & Pharmacokinetics Department, Research Laboratories, Toyama Chemical Co., LTD, Tokyo, Japan.
authors: Takumi
authors: T
authors: Kadota
authors: MediVector, Inc., Cambridge, MA, USA.
authors: Dennis
authors: D
authors: Giesing
authors: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors: Michael H
authors: MH
authors: Court
authors: Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA.
authors: David J
authors: DJ
authors: Greenblatt
mesh_terms: D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D000328:Adult; D000577:Amides / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000577:Amides; D018712:Analgesics, Non-Narcotic; D000998:Antiviral Agents; D011719:Pyrazines; D000082:Acetaminophen; C037386:acetaminophen glucuronide; C462182:favipiravir; C045667:acetaminophen sulfate ester
keywords: acetaminophen; acetaminophen glucuronide; acetaminophen sulfate; drug interactions; favipiravir; paracetamol