• 한국식품영양과학회지
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• 제29권3호
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• pp.448-452
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• 2000

실험동물에서 곰피로부터 분리한 phlorglucinol은 acetaminophen의 투여로 현저히 증가된 간조직에 있어서 지질과선화의 함량을 억제하였다. Acetaminophen 투여에 따른 간 cytochrome P-450, aminopyrine N-deme-thylase 및 aniline hydroxylase 활성변동은 관찰할 수 없었다. 곰피 성분 투여군은 glutathione S-transferase의 활성에서는 대조군의 수준에는 미치지 않으나 효소의 활성이 acetaminophen 단독 투여군보다 현저히 증가되었다. 그리고 간조직중 glutathione의 함량은 phlorglucionl을 전처리군에서 acetaminophen 단독 투여군보다 증가되었다. Glutathione reductase 활성에서는 acetaminophen 투여군은 대조군보다 활성이 감소되었으며, 성분으로 전처리한 군은 acetaminophen 단독 투여군보다 증가 되었다. 따라서 곰피에서 분리한 페놀성화합물인 phloroglucinol은 acetaminophen 투여로 증가되던 지질과 산화함량을 감소시키며, acetaminophen 대사효소활성에서는 glutathione S-transferase의 활성이 증가되어 acetaminophen 의 대사를 촉진시키는 것으로 추정된다.

• 약학회지
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• 제54권3호
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• pp.174-179
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• 2010

Acetaminophen is one of the most commonly used over-the-counter medication in Korea. It is a safe and effective medication for the treatment of mild to moderate pain or fever when used in therapeutic doses. However, acetaminophen overdose is a frequent cause of acute liver failure. The purpose of this study was to evaluate the acetaminophen use for adult patients at community pharmacies in Korea. This study was a 11-questionnaire survey conducted from December 15, 2009 to January 5, 2010. Of the 204 respondents, 117 (57.4%) had used acetaminophen products within 6 months. Only 20 (9.8%) reported having knowledge about the daily maximum doses of acetaminophen, and 3 out of 20 knew it correctly. Only 10 (4.9%) reported having knowledge about the potentialtoxicity of acetaminophen overdose, and 7 out of 10 knew that acetaminophen overdose could cause liver toxicity. The results of this study indicates a need for pharmacists to educate patients regarding the appropriate doses and potential toxicities of acetaminophen.

• 한국식품영양과학회지
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• 제26권6호
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• pp.1173-1180
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• 1997

Hepatotoxicity of caffeine and acetaminophen was investigated in this study. Special attention was paid to the effect of vitamins on the reduction of hepatotoxicity caused by the chemicals. Rat hepaocytes isolated by two-step perfusion method were cultured in two differents methods-suspension, monolayer cultures-, and exposed to caffeine and/or acetaminophen for 24hrs. Caffeine or acetaminophen exhibited no significant hepatotoxicity in terms of intracellular glutathione(GSH) level and lipid peroxidation(MDA), but GSH level was significantly decreased after administrated acetaminophen, and the toxicity caused by the chemicals showed a dose-dependent manner. The synergistic effect of caffeine and acetaminophen was observed when both caffeine and acetaminophen were supplemented to culture medium. At the concentration 1mM, caffeine enhanced the intracellular GSH depletion and MDA formation by 63% and 64%, respectively, compared to single supplementation of 10mM acetaminophen in culture medium. This hepatotoxicity induced membrane integrity loss was observed by lightmicroscope on the simultaneous administration of caffeine and acetaminophen in monolayer cultured hepatocytes. Co-supplementation of vitamins with caffeine/acetaminophen to culture medium results in the protection of hepatocytes from hepatotoxic attach by caffeine/acetaminophen. Especially, vitamin E was superior to vitamin C and $\beta$-carotene from the standpoints of GSH depletion and MDA formation. From this results, it has been speculated that vitamin E may play a role of antioxidant scavenging radicals produced from acetaminophen. Taken all together, in vitro culture system like monolayer culture of hepatocytes may be a useful tool for the evaluation of hepatotoxicity or protection ability of food ingredients.

• BMB Reports
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• 제40권6호
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• pp.1039-1049
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• 2007

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.

• The Korean Journal of Physiology and Pharmacology
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• 제2권2호
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• pp.261-269
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• 1998

Concomitant administration of a single acute dose of ethanol (4 g/kg) protected mice from the hepatocellular injury observed upon administration of a large dose of acetaminophen (400 mg/kg). This was evidenced by the normal histological appearances of liver sections and by the lowered serum aminotransferase activities in mice treated with ethanol and acetaminophen together. In the mice treated with acetaminophen alone, along with the hepatic necrosis, the hepatic microsomal aminopyrine N-demethylase activity was decreased. However, co-administration of ethanol prevented this acetaminophen dependent inhibition on the microsomal mixed function oxidase activity. Pharmacokinetic studies indicated that the concentration of un-metabolized drug in the blood was increased in the ethanol treated mice. Furthermore, upon co-administration of ethanol, although the biliary levels of acetaminophen metabolites (glucuronide, sulfate and cysteine conjugates) were decreased, the level of unmetabolized acetaminophen was increased. Our findings suggest that co-administration of an acute dose of ethanol reduces the degree of hepatocellular necrosis produced by a large dose of acetaminophen and this ethanol dependent protection is, in major part, afforded by suppression of the hepatic microsomal mixed function oxidase activity catalyzing the metabolic activation of acetaminophen.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제30권2호
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• pp.143-149
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• 2004

Background: Some clinical trials have reported that a new analgesic combination of tramadol and acetaminophen provides good efficacy in various pain models. For the more clinical uses of this agent, comparisons about the onset of analgesia and analgesic efficacy in the acute state of pain with the other drugs known as strong analgesics were needed. Purpose: The goal of this study was to compare the times to onset of analgesia and the other analgesic efficacy of 75 mg tramadol/650 mg acetaminophen and 20 mg codeine/500 mg acetaminophen/400 mg ibuprofen in the treatment of acute pain after oral surgery. Patients and Methods: Using a randomized, single-dose, parallel-group, single-center, and active-controlled test design, this clinical study compared the times to onset of analgesia using a two-stopwatch technique and the other analgesic efficacy of the single-dose tramadol/acetaminophen and codeine/acetaminophen/ibuprofen. These were assessed in 128 healthy subjects with pain from oral surgical procedures involving extraction of one or more impacted third molars requiring bone removal. From the time of pain development, the times to onset of perceptible and meaningful pain relief, pain intensity, pain relief, an overall assessment, and adverse events of the study medications were recorded for 6 hours. Results: The demographic distribution and baseline pain data in the two groups were statistically similar. The median times to onset of perceptible pain relief were 21.0 and 24.4 minutes in the tramadol/acetaminophen and codeine/acetaminophen/ibuprofen groups respectively and those to onset of meaningful pain relief were 56.4 and 57.3 minutes, which were statistically similar. The other efficacy variables such as mean total pain relief (TOTPAR) and the sum of pain intensity differences (SPID) were also similar in the early period after pain development and drug dosing. The safety of tramadol/acetaminophen was well tolerated and very comparable to that of codeine/acetaminophen/ibuprofen. Conclusions: In this acute dental pain model, the onset of analgesia and analgesic efficacy of tramadol/acetaminophen was comparable to that of codeine/acetaminophen/ibuprofen. These results showed that tramadol/acetaminophen was recommendable for fast and effective treatment in the management of postoperative acute pain.

• 대한임상독성학회지
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• 제18권2호
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• pp.57-65
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• 2020

Purpose: Since 2012, acetaminophen can be accessed easily not only at pharmacies but also at convenience stores. The relationship between the easy access of acetaminophen and the risk of poisoning has been controversial. Several studies also reported different results regarding the risk of acetaminophen poisoning after access to acetaminophen was relaxed. This study examined the long-term effects on the risk of acetaminophen poisoning after easy access to acetaminophen was implemented. Methods: This was a retrospective analysis of an emergency department (ED)-based in-depth Injury Surveillance Cohort by the Korea Center for Disease Control and prevention from 2011 to 2018. Poisoning cases were selected from the Cohort, and the incidence of acetaminophen poisoning and the characteristics of the cases of acetaminophen poisoning were analyzed. The purchase path and the amount of ingestion in acetaminophen poisoning were sub-analyzed from data of six EDs. Results: Of 57,326 poisoning cases, 4.0% (2,272 cases) were acetaminophen poisoning. Of 2,272 cases of acetaminophen poisoning, 42.8% (974 cases) required in-patient care after ED management. Two hundred and sixty-four of these 964 cases required intensive care. The rates of cases that required in-patient treatment and the rates of cases that required intensive care increased from 29.4% in 2011 to 48.1% in 2018, and from 3.1% in 2011 to 15.2% in 2018, respectively (p<0.001, p<0.001). In the poisoning group with in-depth toxic surveillance (n=15,908), the incidence and proportion of acetaminophen (AAP) poisoning increased from 55 cases per year to 187 cases per year and 4.9% to 6.1%, respectively (p=0.009, p<0.001, respectively). The most common age group of acetaminophen poisoning was teenagers, which is different from the most common age group of other pharmaceutical agents: the middle age group of 40-49 years (p<0.001). Of 15,908 in-depth toxic surveillance patients, 693 patients had AAP poisoning, of whom 377 cases (54.2%) purchased acetaminophen from a non-pharmacy. The proportions of the purchase path from non-pharmacy were 41.4% at 2011-12 and 56.4% (2013-18) (p=0.004). The amount of acetaminophen ingestion was 13.5±14.3 g at 2011-12 and 13.9±15.1 g at 2013-18 (p=0.794). Conclusion: Although the incidence of acetaminophen poisoning did not increase remarkably in the short term after the implementation of the new regulation, the incidence of acetaminophen poisoning has increased slightly during the study period of 2017-18. In addition, the proportion of the purchase path from non-pharmacies has increased since the emergence of new regulations for the easy access of acetaminophen in 2012. The incidence of acetaminophen poisoning might have been affected after the increasing accessibility of acetaminophen in convenience stores. Continuous control of acetaminophen poisoning is required. Furthermore, the prevention of acetaminophen poisoning should be focused on teenagers with specialized school education programs.

• 한국환경보건학회지
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• 제32권5호
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• pp.440-445
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• 2006

통증경감을 위하여 광범위하게 사용되는 acetoaminophen은 치통, 두통에 주로 사용되는 의약물질이다. 의약품의 환경오염과 관련하여 수자원에 유입되는 acetaminophen의 경안천 오염정도를 파악하고 생태 위해성을 평가하기 위하여 본 연구를 수행하였다. 한강 수계이며 용인시와 광주시를 거쳐 팔당호로 흘러 들어가는 경안천(해실교, 수포교, 왕산교, 경안교, 지월교, 광동교, 팔당호)내 acetaminophen 잔류 농도와 분포를 조사하였다. 또한 Daphnia magna를 대상으로 48시간 급성독성평가를 실시하여 위해도를 평가하였다. 잔류의약품 검출을 위해 SPE 추출법을 선택 하였으며, liquid chromatography/mass spectrometry (LC/MS)를 이용하여 분석하였다. 경안천 내에서 acetaminophen 0.439 mg/l이 검출되었다. 독성평가를 실시한 결과, 48시간 $LC_{50}$은 16.9 mg/l로 나타났다. 경안천의 acetamionophen 농도와 독성평가를 바탕으로 위해성 평가를 실시한 결과 위해성은 1 이하였다 하지만 국내에 의약품 발달과 함께 사용이 계속적으로 늘어나는 추세이고, 잔류의약품에 대한 대책이 마련되어있지 않은 이상 수환경은 의약품에 노출될 것이다. 그러므로 잔류의약품이 생태계에 악영향을 미치지 않도록 구체적인 방안이 강구되어야 할 것으로 사료된다.

• 약학회지
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• 제38권5호
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• pp.595-601
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• 1994

Acetaminophen, a widely used analgesic, can be formed by N-acetylation and p-hydroxylation of aniline. Interspecific protoplast fusion technique was used to get acetaminophen directly from aniline and to increase the productivity of acetaminophen. Three auxotrophic mutants were obtained from S. griseus(ATCC 13273) and S. hygroscopicus(KCTC 1089) by N-methyl-N'-nitro-N-nitrosoguanidine(NTG) treatment. Regeneration frequencies of S. griseus$(his^-)$, S. griseus$(lys^-)$, S. hygroscopicus$(arg^-)$ were 42%, 45%, and 31%, respectively. Fusion of protoplasts carrying different auxotrophic markers was achieved by treatment with polyethylene glycol. When protoplasts were treated with 50% polyethylene glycol for 3 minutes, the fusion frequency between S. griseus$(his^-)$ and S. hygroscopicus$(arg^-)$ was $3.8{\times}10^{-5}$. The fusion frequency between S. griseus$(lys^-)$ and S. hygroscopicus$(arg^-)$ was $5.6{\times}10^{-4}$. When we checked the production of acetaminophen, thirty-four out of the fifty-six fusants produced larger amounts of acetaminophen than the parent strains did. Nine fusants produced twice more and twenty-five fusants produced one to two times more of acetaminophen than their parents.

• Archives of Pharmacal Research
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• 제15권1호
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• pp.41-47
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• 1992

In order to obtain acetaminophen, a popular analgesic-antipyretic, though microbial p-hydroxylation and N-acetylation of aniline, various Streptomyces strains were screened. Aniline N-acetylation activity was rather ubiquitous but-hydroxylation activity was selective. Microbial conversion pathway of aniline to acetaminophen was considered to be through N-acetylation and p-hydroxylation or vice versa. However, depending on species used, o-hydroxylation and its degradation activity (S. fradiae) and acetaminophen degradation activity (S. coelicolar) were also detected. Among the screened Streptomyces strains, S fradiae NRRL 2702 showed the highest acetanilide p-hydroxylation activity (203% conversion rate). Furthermore, in S. fradiae carbon source and its concentration, phosphate ion concentration and pH of growth medium were found to play the crucial roles in p-hydroxylation activity. Through the proper combination of factors mentioned above, the ten times more activity (26-30% conversion rate) was attained.