• 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.

• Biomolecules & Therapeutics
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• 제3권3호
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• pp.229-232
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• 1995

In order to study if Glycyrrhizae Radix (GR) has protective effects on hepatotoxicity of acetaminophen in mouse, one of the species which are sensitive to acetaminophen-induced hepatotoxicity, effects of GR on liver weight to body weight ratio, serum alanine and aspartate transaminase (ALT and AST) activities, hepatic UDP-GT2 activity, and histopathologic changes were determined in acetaminophen-treated mice. Liver weight to body weight ratio and UDP-GT2 activity in mouse liver were not altered by GR. However, GR pretreatment lowered serum ALT and AST activities by 77% and 90% respectively, and diminished the degree of centrilobular necrosis caused by acetaminophen in liver as determined by histopathologic observation. These results suggest a possible protective effect of GR against the acetaminophen-induced hepatotoxicity in mice.

• 약학회지
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• 제31권5호
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• pp.286-295
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• 1987

The relationship between in vitro release and in vivo bioavailability of acetaminophen from suppositories was investigated. Effect of glycyrrhizin on the drug release and rectal absorption in rats was also examined. Suppositories containing 25mg of acetaminophen were prepared with Wecobee FS (fatty base) or PEG (water-soluble base) bases. The release from the suppositories were determined with USP rotating basket dissolution apparatus and with the suppository release tester. The temperature of the dissolution medium was very critical for the dissolution of acetaminophen from Wecobee FS suppositories. The bioavailability of acetaminophen was calculated from the plasma concentration-time curve after rectal administration of the suppositories to the rats. There were no significant differences in AUC following rectal administration of Wecobee FS and PEG suppositories, but the release and absorption from the Wecobee FS suppositories were faster than those from PEG suppositories. The dissolution rate obtained by the suppository release tester was better correlated with in vivo absorption rate constant than that by the USP dissolution apparatus. It suggests that the partitioning between rectal fluid and suppository base is the rate-limiting step in the rectal absorption of acetaminophen from suppositories. Glycyrrhizin was found not to affect in vitro dissolution and rectal absorption of acetaminophen.

• 약학회지
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• 제30권6호
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• pp.301-305
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• 1986

Dose-dependent pharmacokinetics of acetaminophen was studied in the rat. Acetaminophen was injected intravenously at doses of 10, 30, 50, 100 and 200mg/kg to the adult male rats. The well-known dose-dependent pharmacokinetic behavior was found even at 30mg/kg dose. It implies that metabolism of acetaminophen in the liver, probably sulfation, is saturated at very low concentration of acetaminophen. Dosage regimen establishment based on this characteristics would be necessary even at usual does level (300-600mg/day/body).

• Journal of Pharmaceutical Investigation
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• 제13권3호
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• pp.89-99
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• 1983

Nylon microcapsules containing acetaminophen could be obtained by interfacial polymerization between sebacoyl chloride and 1, 6-hexamethylenediamine. Methylcellulose affected the micromeritic properties and dissolution characteristics of microcapsules. The particle size distribution was affected by the stirring speed and viscosity grade of methylcellulose. The surface observed by the scanning electron microscopy was affected by the methylcellulose. Nylon microcapsules produced in above method containing acetaminophen exhibited the retarded dissolution in comparison with uncoated acetaminophen. Release of acetaminophen from microcapsules decreased with decreasing pH of medium and with increasing the viscosity grade of methylcellulose and stirring speed.

• 약학회지
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• 제30권2호
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• pp.100-103
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• 1986

The second derivative absorption spectra of acetaminophen in commercial tablet forms were measured without prior separation from other pharmaceutical adjuvants. The second derivative spectra of acetaminophen were found to have no influence on the characteristic absorbance band of it. A plot of 25 sets of the ordinate (Z) values with various acetaminophen concentrations mixed in other additives gave a straight line (correlation coefficient, 0.9999) and the slope was 2.901${\times}10^{-2}Z$ value/($\mu\textrm{g}$/ml). The procedures were sufficiently sensitive, precise and economical for the assay of tablets of acetaminophen.

• 약학회지
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• 제28권1호
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• pp.17-20
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• 1984

Synthetic procedures to synthesize fenbufen-acetaminophen ester were searched by acid chloride method, DCC method and mixed acid anhydride method. The compound was synthesized by DCC method and mixed acid anhydride method but could not be synthesized by acid chloride method. Its anti-inflammatory activity was superior to acetaminophen and similar to fenbufen.

• 대한임상독성학회지
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• 제15권2호
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• pp.94-100
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• 2017

Purpose: Acute acetaminophen intoxication is a common occurrence that can cause lethal complications. In most domestic emergency departments, clinicians tend to treat acetaminophen intoxication based on patients' history alone, simply due to the lack of a rapid acetaminophen laboratory test. We performed a 20-month study of intoxication patients to determine the correlation between the history of patients and serum laboratory tests for acetaminophen. Methods: We took blood samples from 280 intoxication patients to evaluate whether laboratory findings detected traces of acetaminophen in the sample. Patients were then treated according to their history. Laboratory results came out after patients' discharge. Agreement between patients' history and laboratory results were analyzed. Results: Among the 280 intoxicated patients enrolled, 38 patients had positive serum acetaminophen concentrations; 18 out of 38 patients did not represent a history suggesting acetaminophen intoxication. One patient without the history showed toxic serum acetaminophen concentration. Among the patients with the history, two patients with toxic serum acetaminophen concentration did not receive N-acetylcysteine (NAC) treatment due to their low reported doses, while other 2 patients without significant serum acetaminophen concentration did receive NAC treatment due to their high reported doses. Conclusion: This study showed a good overall agreement between history and laboratory test results. However, some cases showed inconsistencies between their history and laboratory test results. Therefore, in treating intoxication patients, a laboratory test of acetaminophen with rapid results should be available in most domestic emergency departments.

• Bulletin of the Korean Chemical Society
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• 제31권12호
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• pp.3663-3667
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• 2010

Acetaminophen (N-acetyl-p-aminophenol) is one of the most popular analgesic and antipyretic drugs. An isotope dilution mass spectrometric method based on LC/MS was developed as a candidate reference method for the accurate determination of acetaminophen in pharmaceutical product. After spiking an isotope labeled acetaminophen (acetyl-$^{13}C_2$, $^{15}N$-acetaminophen) as an internal standard, tablet extracts were analyzed by LC/MS in a selected reaction monitoring (SRM) mode to detect ions at m/z $152{\rightarrow}110$ and m/z $155{\rightarrow}111$ for acetaminophen and acetyl-$^{13}C_2$, $^{15}N$-acetaminophen, respectively. The repeatability and reproducibility of the developed ID/LC-MS method were tested for the validation and assessment of metrological quality of the method.

• 대한한의학방제학회지
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• 제16권2호
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• pp.183-191
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• 2008

Acetaminophen (N-acety1-p-aminophenol, paracetamol) is widely used as an over-the-counter analgesic and antipyretic drug. Intake of a over dose of acetaminophen may result in severe hepatic necrosis. In this study, we investigated the liver damage in mice using single dose (300 mg/kg) of acetaminophen and the possible protective effects of administration (50-200 mg/kg body weight) of SB-Ex on acetaminophen-induced liver damage in mice. The alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were determined in the plasma of mice. The effect of SB-Ex on lipid peroxidation product thiobarbituric reacting substances (TBARS) and some antioxidant enzymes superoxide dismutase (SOD), catalase, d-aminolevulinate dehydratase (${\sigma}$-ALA-D) activities, and gluthathione peroxidase (GPx), were also evaluated in the mouse liver homogenate. Acetaminophen caused liver damage as evident by statistically significant increased in plasma activities of AST and ALT. There were general statistically significant losses in the activities of SOD, catalase, ${\sigma}$-ALA-D, and GPx and an increase in TBARS in the liver of acetaminophen-treated group compared with the control group. However, SB-Ex was able to counteract these effects. These results suggest that SB-Ex can act as hepatoprotectives against acetaminophen toxicity and is a good candidate for further evaluation as an effective chemotherapeutic agent.