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J Clin Pharmacol. 2019 May 14. doi: 10.1002/jcph.1439. [Epub ahead of print]

Pharmacokinetic Analysis and Biomarker-Assisted Safety Assessment of Acetaminophen in Combination With Ojeok-san Compared With Acetaminophen Alone.

Park SI1,2, Park JY3, Lee JH4,5,6, Park MS7, Lee KT8,9, Yim SV1,4, Yoon YR10, Kim BH1,2,4,6.

Author information

1
Department of Clinical Pharmacology and Therapeutics, Kyung Hee University Hospital, Seoul, Republic of Korea.
2
East-West Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea.
3
Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
4
Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
5
Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul, Republic of Korea.
6
Department of Biomedical Science and Technology, Kyung Hee University, Seoul, Republic of Korea.
7
Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
8
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
9
Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
10
School of Medicine, Kyungpook National University and Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea.

Abstract

Acetaminophen and Ojeok-san are both frequently used analgesics. In this study, we evaluated acetaminophen pharmacokinetics (PK) and changes in microRNA-122 (miR-122) levels after multiple dosing of acetaminophen with or without Ojeok-san. An open-label, 1-sequence, 2-period, 2-treatment crossover study was conducted in 18 subjects. In period 1, 500 mg of acetaminophen was administered 3 times on day 1 and once on day 2. In period 2, after the administration of 14.47 g of Ojeok-san twice on day 2 and 3 times daily on days 3 to 7, Ojeok-san and acetaminophen were coadministered 3 times each on day 8 and once each on day 9. The geometric mean ratios (90% confidence intervals) of acetaminophen with Ojeok-san to acetaminophen alone were 0.98 (0.87 to 1.10) and 1.02 (0.98 to 1.05) for the maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve during the dosing interval (AUC0-τ ), respectively, of acetaminophen at steady state. The alanine aminotransferase (ALT) levels were within the reference range in all the participants throughout the study period, although the mean fold changes in both serum miR-122 and ALT levels from baseline tended to increase on days 2 to 5. In conclusion, the PK properties of acetaminophen were not significantly affected by Ojeok-san coadministration. For osteoarthritis patients taking acetaminophen with or without Ojeok-san, monitoring potential liver toxicity using miR-122 as a biomarker may be useful.

KEYWORDS:

acetaminophen; biomarkers; drug-induced liver injury; herbal drugs; pharmacokinetics

PMID:
31090078
DOI:
10.1002/jcph.1439

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