TY - JOUR
T1 - Baseline uric acid levels and steady-state favipiravir concentrations are associated with occurrence of hyperuricemia among COVID-19 patients
AU - Koseki, Takenao
AU - Nakajima, Kazuki
AU - Iwasaki, Hitoshi
AU - Yamada, Shigeki
AU - Takahashi, Kazuo
AU - Doi, Yohei
AU - Mizuno, Tomohiro
N1 - Funding Information:
This research was supported by grants from the Japan Agency for Medical Research and Development (AMED) under grant numbers 19fk0108150s0001 and 20fk0108150s0001.
Funding Information:
This research was supported by grants from the Japan Agency for Medical Research and Development (AMED) under grant numbers 19fk0108150s0001 and 20fk0108150s0001. YD has served on a scientific advisory board of, and received a speaking fee from, FujiFilm Toyama Chemical, the manufacturer of favipiravir in Japan. The other authors declare that they have no conflicts of interest. This study was approved by the Institutional Review Board of Fujita Health University (HM20-169). TK, YD, and TM conceived and designed the study. KN and HI performed the experimental work. TK and TM contributed to the statistical analysis. SY and KT contributed to the study concept and design. TK, YD, and TM drafted the manuscript. All authors contributed to the critical input and endorsed the final version of the manuscript. The authors would like to thank Masahiro Suzuki for helping with the processing of serum samples, and Eishi Imoto (Shimadzu Corporation) for validating the LC-MS method for quantifying FVP.
Publisher Copyright:
© 2021 The Authors
PY - 2022/2
Y1 - 2022/2
N2 - Objectives: Favipiravir is an antiviral that is being evaluated for the treatment of COVID-19. Use of favipiravir is associated with elevation of serum uric acid levels. Risk factors for the occurrence of hyperuricemia are unclear. Methods: Specimens from COVID-19 patients who received 10 days of favipiravir in a previous clinical trial (jRCTs041190120) were used. Serum favipiravir concentrations were measured by LC-MS. Factors associated with the development of hyperuricemia were investigated using logistic regression analysis. Optimal cut-off values for the baseline serum uric acid levels and steady-state serum favipiravir concentrations in predicting the occurrence of hyperuricemia were determined by ROC curve analysis. Results: Among the 66 COVID-19 patients who were treated with favipiravir for 10 days, the steady-state serum favipiravir concentrations were significantly correlated with serum uric acid levels. High baseline serum uric acid levels and steady-state serum favipiravir concentrations during therapy were factors associated with the development of hyperuricemia. The cut‑off baseline serum uric acid level and steady-state serum favipiravir concentration during favipiravir administration determined to predict hyperuricemia were 3.7 mg/dL and 46.14 μg/mL, respectively. Conclusions: Patients with high baseline serum uric acid levels or who achieved high steady-state serum favipiravir concentrations during therapy were susceptible to hyperuricemia.
AB - Objectives: Favipiravir is an antiviral that is being evaluated for the treatment of COVID-19. Use of favipiravir is associated with elevation of serum uric acid levels. Risk factors for the occurrence of hyperuricemia are unclear. Methods: Specimens from COVID-19 patients who received 10 days of favipiravir in a previous clinical trial (jRCTs041190120) were used. Serum favipiravir concentrations were measured by LC-MS. Factors associated with the development of hyperuricemia were investigated using logistic regression analysis. Optimal cut-off values for the baseline serum uric acid levels and steady-state serum favipiravir concentrations in predicting the occurrence of hyperuricemia were determined by ROC curve analysis. Results: Among the 66 COVID-19 patients who were treated with favipiravir for 10 days, the steady-state serum favipiravir concentrations were significantly correlated with serum uric acid levels. High baseline serum uric acid levels and steady-state serum favipiravir concentrations during therapy were factors associated with the development of hyperuricemia. The cut‑off baseline serum uric acid level and steady-state serum favipiravir concentration during favipiravir administration determined to predict hyperuricemia were 3.7 mg/dL and 46.14 μg/mL, respectively. Conclusions: Patients with high baseline serum uric acid levels or who achieved high steady-state serum favipiravir concentrations during therapy were susceptible to hyperuricemia.
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U2 - 10.1016/j.ijid.2021.12.324
DO - 10.1016/j.ijid.2021.12.324
M3 - Article
C2 - 34910957
AN - SCOPUS:85122204503
VL - 115
SP - 218
EP - 223
JO - International Journal of Infectious Diseases
JF - International Journal of Infectious Diseases
SN - 1201-9712
ER -