88ORIGINAL Seung-Min ARTICLE Yeom, et al. Various Ways to Prevent Toxicity of Non-steroidal Anti Inflammatory Drugs Korean J Clin Lab Sci. 2017;49(2):88-98 https://doi.org/10.15324/kjcls.2017.49.2.88 pISSN 1738-3544 eISSN 2288-1662 A Methocarbamol Combination to Prevent Toxicity of Non-steroidal Anti Inflammatory Drugs Seung-Min Yeom1,2, Min-Seok Kim1,3, Eric Lingenfelter1,4, Jonathan Broadwell5 1USFK, Army 2nd Infantry Division, Camp Hovey Combined Troops Medical Aid Station, Dongducheon, Korea 2College of Pharmacy, Woo-suk University, Jeonju, Korea 3College of Nursing, Chung-Ang University, Seoul, Korea 4Defense Health Agency, Washington, USA 5Army National Guard, University of Utah School of Medicine, Salt Lake, USA 비스테로이드성 항염증제의 약물독성 예방을 위한 Methocarbamol의 약물조합 염승민1,2, 김민석1,3, Eric Lingenfelter1,4, Jonathan Broadwell5 1주한미군 육군 제2보병사단 캠프호비 클리닉, 2우석대학교 약학대학, 3중앙대학교 간호대학, 4미국 국방보건국, 5미국 주방위군, 유타대학교 의과대학 To prevent toxicity from both robax platinum (methocarbamol, ibuprofen) and robaxacet (methocarbomol, acetaminophen), separately, we used stretches and naproxen as a non-steroidal anti-inflammatory drug (NSAID) to compare each effectiveness. This study used the United States Forces Korea Prescription form (Annex A-Over-The-Counter Prescription) and Alice Rich’s Pain scale with robax platinum, robaxacet including narproxen. The IBM SPSS statics version 24 was used to calculate the data. The combined methocarbamol 500 mg, acetaminophen 325 mg tablet, and ibuprofen 200 mg (or naproxen) tablet can work as well as the combined methocarbamol 500 mg tablet with acetaminophen 325 mg tablet with stretches. Both methods were successful in managing pain. The drug combination of methocarbamol 500 mg, acetaminophen 325 mg and Corresponding author: Seung-Min Yeom ibuprofen 200 mg tablets yielded similar benefits as the methocarbamol 500 mg and USFK, Army 2nd Infantry Division, Camp Hovey acetaminophen 325 mg tablets paired with physical stretching exercises regarding managing Combined Troops Medical Aid Station, 2557 Pyeonghwa-ro, Dongducheon 11311, Korea overall pain. Tel: 82-31-298-7655 Fax: 82-31-298-7656 Key words: Methocarbamol, NSAID, Stretches, Toxicity E-mail: [email protected] This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License Received: March 14, 2017 (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in Revised 1st: April 4, 2017 any medium, provided the original work is properly cited. Revised 2nd: April 4, 2017 rd Copyright © 2017 The Korean Society for Clinical Laboratory Science. All rights reserved. Revised 3 : April 14, 2017 Revised 4th: April 16, 2017 Revised 5th: April 16, 2017 Accepted: April 17, 2017 INTRODUCTION treatments are needed because of each patient has certain underlying diseases such as gastrointestinal, cardiovascular The patients on the professional athletic background and any specific others. As part of personalized medicine, such as military service members are directly exposed to targeted treatment is necessary as one of the important musculoskeletal disorders. In case of muscle pain, the ways to alleviate pain. To avoid overdose and prevent each more various pains occur, the more personalized medicine toxicity, various types of pain treatments such as www.kjcls.org Korean J Clin Lab Sci. Vol. 49, No. 2, June 2017 89 additional exercise should be considered to treat them. If the dose-dependent perturbations in urinary metabolite patients take amount of over the counter, they could concentrations caused by naproxen toxicity. These were possibly be overdosage. As part of targeted treatment, the investigated by using 1H NMR spectroscopy coupled with following results are considered to be one of the important multivariate statistical analysis [3]. Histopathologic evalu- ways to study toxicity. According to the following stack ation of naproxen-induced acute gastrointestinal damage plot of nuclear magnetic resonance spectra (NMR) (Figure in rats demonstrated a significant dose-dependent effect. 1), the targeted experiment showing characteristics of Furthermore, principal component analysis (PCA) of 1H metabolic fingerprints with tissue-specific toxicity NMR from rat urine revealed a dose-dependent metabolic produced by different site-selective toxicity such as shift between the vehicle-treated control rats and rats xenobiotics. It was given in single doses to rats in relation treated with low-dose (10 mg/kg body weight), mode- to an untreated control. In this case, by using 600-MHz rate-dose (50 mg/kg), and high-dose (100 mg/kg) naproxen, which most precise frequency to investigate specific coinciding with their gastric damage scores after chemical resonance result from metabolic pathway on naproxen administration [3]. The resultant metabolic NMR test, each 600-MHz spectrum represents one time profiles demonstrate that the naproxen-induced gastric point after dosing for each toxic compound [1]. It can damage exhibited energy metabolism perturbations that show the toxicity on xenobiotics relatively affect specific elevated their urinary levels of citrate, cis–aconitate, regions within the organs (depicted in the figure by shaded creatine, and creatine phosphate. These findings demon- boxes): puromycin affects the renal glomeruli; uranyl strate that 1H NMR-based urinary metabolic profiling can nitrate affects the lower regions of proximal tubules and facilitate noninvasive and rapid diagnosis of drug side others such as result that 2-bromoethanamine affects effects and is suitable for elucidating possible biological renal medulla, including loop of Henle and collecting pathways perturbed by drug toxicity [3-6]. ducts; and hydrazine affects hepatic parenchymal cells Therefore, As part of personalized medicine, targeted [1,2]. Therefore, it’s necessary to treat patients based on treatment is necessary as various types of pain treatments. patient’s underlying diseases. For instance, prescription including stretches can be used In case of another chemical tracking [3], we could see to treat patients are at risk of over dosage. Not only prescribed drugs but also over the counter drugs have to be considered in case of treatment for patients who have a various musculoskeletal pains on individual underlying diseases for a long term. According to previous study about hydrocodone with ibuprofen [7], it can show analgesic combination can be much effective than single analgesic. MATERIALS AND METHODS 1. Pain scale To measure the pain, we used Alice Rich’s ‘0∼10 Comparative Pain Scale’ [8]. 2. Examed term Figure 1. The result of pain reliefs combination with each In this study, the following record was performed on methocarbamol, acetaminophen, naproxen or ibuprofen and stretch. Declaration of Helsinki. All 90 patients who visited the www.kjcls.org 90 Seung-Min Yeom, et al. Various Ways to Prevent Toxicity of Non-steroidal Anti Inflammatory Drugs United States Army Camp Hovey clinic from June 14, 2016 acetaminophen was identified to be N-acetyl-p-ben- to September 23, 2016, with muscle pain including back zoquinone imine (NAPQI). It was found to be formed by pain. The patients were divided into two groups according cytochrome P-450 (CYP) by a direct two electron oxi- to the level of pain and severity. The numerical value was dation of acetaminophen, a previously unrecognized calculated from mild, moderate, severe based on 0 to 10. mechanism of CYP [15]. The CYP isoforms important in This exam is officially confidential information and got acetaminophen metabolism have been shown to be authorized to record on system and research associated CYP2E1, CYP1A2, CYP3A4, and CYP2D6 [16]. Aceta- with ‘Declaration of Helsinki’. The researchers properly minophen activation by human liver cytochromes P450IIE1 dealt with pain reliefs. and P450IA2 [17] and covalent binding of acetaminophen to protein was found to correlate with P450IA2 [17], 3. NSAIDs and Methocarbamol, Acetaminophen acetaminophen-induced hepatotoxicity [18]. This study used the United States Forces Korea Pre- Therefore, above data can show none of them is overlap scription form (Annex A-Over-The-Counter prescription) with acetaminophen, naproxen (or ibuprofen) and with robax platinum, robaxacet and naproxen including methocarbamol. So we combined each group selectively paracetamol and ibuprofen. to group1, 2 and 3. Each group indicate certain combi- nation such as following. The group 1 received acetami- 4. Making pain relief combination based on metabolic nophen 325 mg tablets (2 pills, 8 hr×7 days)+ibuprofen pathways 200 mg tablets (1 pill, 8 hr×7 days). The group 2 received Methocarbamol is the carbamate of guaifenesin, but acetaminophen 325 mg tablets (2 pills, 8 hr×7 does not produce guaifenesin as a metabolite, because the days)+methocarbamol 500 mg tablets (1 pill, 8 hr×2 carbamate bond is not hydrolyzed metabolically; meta- days)+naproxen or ibuprofen 200 mg (1 pill, 8 hr×7 days). bolism is by Phase I ring hydroxylation and O-demethylation, The group 3 received acetaminophen 325 mg tablet (2 followed by Phase II conjugation. All the major metabo- pills, 8 hr×7 days)+methocarbamol 500 mg (1 pill, 8 hr×2 lites are unhydrolyzed carbamates [9,10]. days)+stretches (3 times a day, every 8 hr×7 days). Acetaminophen (paracetamol) is metabolised primarily in the liver, into toxic and non-toxic products. Three 5. Dosage metabolic pathways are notable according to research of According to the U.S. Food and Drug Administration