We developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of acetaminophen concentration in human plasma. Following protein precipitated extraction, the analytes were separated and analyzed using an UPLC-MS/MS in the multiple reaction monitoring (MRM) mode with the respective [M+H]+ ions, m/z 152.06 → 110.16 for acetaminophen and m/z 180.18 → 138.12 for phenacetin (internal standard, IS). The method showed a linear response from 1 to 100 µg/mL (r > 0.9982). The limit of quantitation for acetaminophen in plasma was 1 µg/mL. The intra- and inter-day accuracy ranged in the ranges of 94.40–99.56% and 90.00–99.20%, respectively. The intra- and inter-day precision ranged in the ranges of 2.64–10.76% and 6.84–15.83%, respectively. This method was simple, reliable, precise and accurate and can be used to determine the concentration of acetaminophen in human plasma. Finally, this fully validated method was successfully applied to a pharmacokinetic study of acetaminophen in healthy volunteers following oral administration.
Acetaminophen* ; Administration, Oral ; Healthy Volunteers ; Humans* ; Ions ; Mass Spectrometry ; Phenacetin ; Plasma*

PURPOSE: Serious acetaminophen (AAP) poisoning causes hepatotoxicity. N-acetylcysteine (NAC) is the most effective therapy for AAP poisoning and can be administered orally and intravenously (IV). Several studies have compared the efficacy of these two routes of administration and the results have been controversial. The purpose of this study was to compare the efficacy of oral and IV NAC for the prevention of hepatic toxicity in Korean patients whose serum AAP levels were higher than normal. METHODS: A retrospective before/after study was performed, in which the patients presented to the emergency department with an AAP overdose from February 1995 to March 2012. A 3-day oral NAC regimen was used in the beginning, and a 20-hr intravenous regimen was then used from 2007. This study assessed the complications of an AAP overdose, such as hepatotoxicity, hepatic failure and renal failure as well as the side effects of the treatment regimen. RESULTS: A total of 41patients was enrolled in this study. The median ALT and AST were 63 (IU/L) and 57 (IU/L) for the oral NAC treated patients, and 14 (IU/L) and 20 (IU/L) for the IV NAC treated patients (p=0.004 and p=0.001, respectively). The incidence of complications was similar in the treatment groups (p=0.399). Among the patients, 7 patients developed hepatotoxicity and were treated successfully with oral or IV NAC. CONCLUSION: This study suggests that IV NAC and oral NAC can prevent and successfully treat hepatic toxicity in patients whose serum AAP levels are higher than normal.
Acetaminophen ; Acetylcysteine ; Administration, Intravenous ; Emergencies ; Humans ; Incidence ; Liver Failure ; Oligopeptides ; Renal Insufficiency ; Retrospective Studies

PURPOSE: The purpose of this study was to develop therapeutic decision guidelines on N-acetylcysteine (NAC) treatment for acetaminophen (AAP) overdose in a situation where a serum level determination is not available within 8 hours. METHODS: We reviewed retrospectively the medical records of patients admitted for AAP overdose from January 2001 to February 2004. Forty-nine patients met inclusion criteria; patients with acute AAP overdose who were exposed to 7.5 g or 140 mg/kg or greater, determination of the serum level was not available within 8 hours, and NAC treatment was started empirically before identification of the serum level. The patients had been treated with a 72hour oral or a 20hour intravenous (IV) NAC treatment protocol. RESULTS: Patients were classified into an Oral NAC (n=24) group and an IV NAC (n=25) group based on the treatment protocol. There were no significant intergroup differences in patient characteristics, time variables, distribution of risk categories, and hepatotoxicity. All the patients in both toxic groups were fully recovered, and the difference in the number of adverse reactions during NAC treatment were not significant between the two groups (Oral NAC vs IV NAC, 4 (16%) vs. 2 (8%), respectively; p=0.417). The numbers of patients who discontinued the NAC treatment were 14 (58%) in the Oral NAC group and 8 (32%) in the IV NAC group (p=0.088). The six patients in the nontoxic category of IV NAC group were already completed before determination of the serum level. CONCLUSION: Therapeutic decisions for AAP overdose which are based entirely on ingestion history have some limitations. IV NAC is as effective as oral treatment for patients with acute AAP overdose. If the serum level is not available within 8 hours, the clinician should preventively administer the first dose of oral NAC to patients without severe vomiting. Subsequently, when the serum level is determined, the need for additional therapy should be determined to reduce unnecessary use of NAC. However, if the patients present with severe vomiting or contraindications to oral treatment, intravenous administration is required.
Acetaminophen* ; Acetylcysteine* ; Administration, Intravenous ; Clinical Protocols ; Eating ; Humans ; Medical Records ; Retrospective Studies ; Vomiting

Acetaminophen ; administration & dosage ; poisoning ; Acetylcysteine ; administration & dosage ; pharmacology ; therapeutic use ; Brunei ; Drug Overdose ; drug therapy ; physiopathology ; Humans

BACKGROUND: Hepatic necrosis after acetaminophen overdose results from the increased formation of a highly toxic intermediatc(N-acetyl-p-benzoquinoneimine), produced by acetaminophen metabolism through the cytochrome P450 mixed function oxidase system. N-acetyl-p-benzoquinoneimine is normally detoxified by endogenous glutathione, but the increased production induced by an acetaminophen overdose may depletc glutathione stores, allowing the intermediate to react with and to destroy hepatocytes. METHOD & MATERIAL: We have estimated the hepatoprotective effects of 4-methylpyrazole(500mg/kg and 50mg/kg), inhibitor of cytochrone P450 isoenzyme, when given at two hours after single oral overdose of acetaminophen(2,000mg/kg) in rats. RESULTS: As far as overall protective effect of 4-methylpyrazole on hepatic necrosis score concerned, seam transaminase(AST, ALT) level were found to be decreased in 4-methylpyrazole-treated group compared to untreated group after acetaminophen overdose. No consistent difference in hepatoprotective effect was demonstrated between rats with high dose of 4-methylpyazole(500mg/kg) and rats with lower dose of 4-methylpyrazole(50mg/kg). CONCLUSION: We concluded that oral administration of 4-methylpyrazole apperas to protect hepatotoxicity effectively to acetaminophen overdose.
Acetaminophen* ; Administration, Oral ; Animals ; Cytochrome P-450 Enzyme System ; Glutathione ; Hepatocytes ; Metabolism ; Models, Animal* ; Necrosis ; Oxidoreductases ; Rats*

BACKGROUND: Prostaglandin inhibitors have been successfully used to inhibit some types of postoperative pain and reduce opioids requirements in others. Antiprostaglandin activity may be ineffective unless the preparations are given at the appropriate time before surgery. This study aimed to determine if the intrarectal administration of acetaminophen immediately before surgery would markedly reduce pain in the postoperative period. METHODS: The children were divided to two groups. Each group was consisted of 15 children. The children in control group were administered intramuscularly glycopyrrolate(0.004 mg/kg) 20 minute. The children in experimental group were administered glycopyrrolate(0.004 mg/kg) intramuscularly and were administered acetaminophen(250 mg) rectally 20 minute before the children were taken to the operating theatre. RESULTS: In the recovery room, the children who had recived acetaminophen were signifcantlly quieter (p<0.01), agitated less(p<0.01) and cried less(p<0.01) painless(p<0.01) than those nonadministered group. There were no obvious differnces between the groups in intra-operative bleeding (as estimated by the surgeon), or in measured blood loss. No postopertive complications become evident. CONCLUSIONS: The preoperative rectal administration of acetaminophen for pain relief after tonsillectomy is safe and effective.
Acetaminophen* ; Administration, Rectal ; Analgesics, Opioid ; Child* ; Dihydroergotamine ; Hemorrhage ; Humans ; Pain, Postoperative* ; Postoperative Period ; Prostaglandin Antagonists ; Recovery Room ; Tonsillectomy*

INTRODUCTIONParacetamol overdose is the most common drug overdose worldwide. To our knowledge, the maximum number of paracetamol tablets ingested reported in the literature is 45 g.

CLINICAL PICTUREWe describe a 21-year-old patient who acutely ingested 120 tablets, each 500 mg paracetamol (i.e., 60 g equivalent to 1200 mg/kg body weight) in a suicidal attempt. Our patient also drank 2 bottles of codeine-based cough syrup equivalent to 360 mg of codeine. At 6 hours post ingestion, her serum paracetamol level was 207 mg/L. The poor prognostic factors for paracetamol overdose in our patient included massive paracetamol ingestion (confirmed by blood levels), codeine co-ingestion and elevated serum amylase (189 U/L).

TREATMENTShe was treated with a 3-day modified regimen of intravenous N-acetylcysteine.

OUTCOMEThe liver function tests and the prothrombin time remained normal over the second and third day of admission and the patient was discharged without complications on the fifth day.

CONCLUSIONFrom this experience we feel that in very severe paracetamol poisoning, a modified regime of intravenous N- acetylcysteine for 3 days is safe and efficacious.

Acetaminophen ; blood ; poisoning ; Acetylcysteine ; administration & dosage ; Adult ; Amylases ; blood ; Antidotes ; administration & dosage ; Codeine ; poisoning ; Drug Overdose ; Female ; Humans ; Liver Function Tests ; Narcotics ; poisoning ; Suicide, Attempted ; Tablets ; Time Factors

AIMTo report a series of varicocelectomy performed under pure local anesthesia.

METHODSFrom July 1988 to June 2003, a total of 575 patients, aged between 15 and 73 years, underwent high ligation of the internal spermatic vein for treatment of a varicocele testis under a regional block in which a precise injection of 0.8 % lidocaine solution was delivered to involved tissues after exact anatomical references were made. A 100-mm visual analog scale (VAS) was used to assess whether the pain level was acceptable.

RESULTSThe surgeries were bilateral in 52 cases, and unilateral in 523 cases. All were successfully performed on an outpatient basis except in the case of two patients, who were hospitalized because their surgeries required general anesthesia. Overall, 98.6 % (567/575) of men could go back to work by the end of the first post-operative week and only 8 (1.4 %) men reported feeling physical discomfort on the eighth day. The VAS scores varied from 11 mm to 41 mm with an average of (18.5+/-11.3) mm that was regarded as tolerable.

CONCLUSIONThis study has shown varicocelectomy under local anesthesia to be possible, simple, effective, reliable and reproducible, and a safe method with minimal complications. It offers the advantages of more privacy, lower morbidity, with no notable adverse effects resulting from anesthesia, and a more rapid return to regular physical activity with minor complications.

Acetaminophen ; administration & dosage ; Adolescent ; Adult ; Aged ; Analgesics, Non-Narcotic ; administration & dosage ; Anesthesia, Local ; Anesthetics, Local ; administration & dosage ; Follow-Up Studies ; Humans ; Lidocaine ; administration & dosage ; Male ; Middle Aged ; Outpatients ; Pain, Postoperative ; drug therapy ; Postoperative Complications ; Varicocele ; surgery ; Vascular Surgical Procedures ; methods

PURPOSE: Transrectal ultrasound-guided prostate biopsy is the procedure of choice for diagnosing prostate cancer. We compared with pain-relieving effect of acetaminophen, a known drug for enhancing the pain-relieving effect of tramadol, and eutectic mixture of local anesthetics (EMLA), a local anesthetic agent, with that of the conventional periprostatic nerve block method. MATERIALS AND METHODS: This was a prospective, randomized, single-blinded study. A total of 430 patients were randomly assigned to three groups. Group 1 received a periprostatic nerve block with 1% lidocaine, group 2 received acetaminophen 650 mg, and group 3 received EMLA cream for pain control. All patients were given 50 mg of tramadol intravenously 30 minutes before the procedure. At 3 hours after completion of the procedure, the patients were asked to grade their pain on a horizontal visual analogue scale (VAS). The patients were also asked whether they were willing to undergo future biopsy if required. RESULTS: There were no significant differences between the three groups in terms of age, prostate-specific antigen, prostate size, or numbers of biopsy cores. The pain scores for groups 2 and group 3, which were 3.47+/-1.92 and 3.50+/-1.36, respectively, were similar and were significantly lower than that of group 1, which was 5.24+/-2.07. CONCLUSIONS: Acetaminophen and EMLA cream with intravenous injection of tramadol are safe, easy, and effective methods of controlling pain during the procedure. These methods were more effective for pain relief than was the conventional periprostatic nerve block method.
Acetaminophen ; Administration, Oral ; Anesthetics, Local ; Biopsy ; Biopsy, Needle ; Humans ; Injections, Intravenous ; Lidocaine ; Nerve Block ; Prilocaine ; Prospective Studies ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms ; Tramadol

The disposition kinetics of levofloxacin was investigated in six male crossbred calves following single intravenous administration, at a dose of 4 mg/kg body weight, into the jugular vein subsequent to a single intramuscular injection of paracetamol (50 mg/kg). At 1 min after the injection of levofloxacin, the concentration of levofloxacin in plasma was 17.2 +/- 0.36 microgram/ml, which rapidly declined to 6.39 +/- 0.16 microgram/ml at 10 min. The drug level above the MIC90 in plasma, was detected for up to 10 h. Levofloxacin was rapidly distributed from blood to the tissue compartment as evidenced by the high values of the distribution coefficient, alpha (17.3 +/- 1.65 /h) and the ratio of K12/K21 (1.83 +/- 0.12). The values of AUC and Vdarea were 12.7 +/- 0.12 microgram.h/ml and 0.63 +/- 0.01 l/kg. The high ratio of the AUC/MIC (126.9 +/- 1.18) obtained in this study indicated the excellent antibacterial activity of levofloxacin in calves. The elimination half-life, MRT and total body clearance were 1.38 +/- 0.01 h, 1.88 +/- 0.01 h and 0.32 +/- 0.003 l/kg/h, respectively. Based on the pharmacokinetic parameters, an appropriate intravenous dosage regimen for levofloxacin would be 5 mg/kg repeated at 24 h intervals when prescribed with paracetamol in calves.
Acetaminophen/administration & dosage/*pharmacokinetics ; Animals ; Anti-Bacterial Agents/administration & dosage/blood/*pharmacokinetics ; Area Under Curve ; Cattle/*metabolism ; Drug Therapy, Combination ; Half-Life ; Hybridization, Genetic ; Injections, Intravenous/veterinary ; Male ; Ofloxacin/administration & dosage/blood/*pharmacokinetics ; Time Factors