A prospective, population-based study of acute ibuprofen overdose: Complications are rare and routine serum levels not warranted

McElwee, Newell E.; Veltri, Joseph C.; Bradford, David C.; Rollins, Douglas E.

doi:10.1016/s0196-0644(05)82471-0

Cited by 51 publications

(29 citation statements)

References 7 publications

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“…For example, significant side effects are seen with ibuprofen, including those of the central nervous system (McElwee et al, 1990), gastrointestinal tract (Lanza, 1984), liver (Riley and Smith, 1998), and respiratory tract (Antonicelli and Tagliabracci, 1995). On the other hand, little has been accomplished over the same period of time for the treatment of advanced colon cancer, with its mortality remaining essentially unchanged for at least three decades (American Chemical Society, 2008).…”

Section: Introductionmentioning

confidence: 99%

Phospho-Ibuprofen (MDC-917) Is a Novel Agent against Colon Cancer: Efficacy, Metabolism, and Pharmacokinetics in Mouse Models

Xie¹,

Sun²,

Tang³

et al. 2011

J Pharmacol Exp Ther

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We have developed a novel chemical modification of conventional nonsteroidal anti-inflammatory drugs to reduce their toxicity and enhance their efficacy. Phospho-ibuprofen [(PI) 2-(4-isobutyl-phenyl)-propionic acid-4-(diethoxy-phosphoryloxy)-butyl ester (MDC-917)], a novel derivative of ibuprofen, strongly inhibited the growth of human colon cancer cells in vitro and SW480 human colon cancer xenografts in nude mice. PI was metabolized minimally by cultured cells, but extensively by liver microsomes and mice, undergoing regioselective oxidation to produce 1-OH-PI and carboxyl-PI, which can be hydrolyzed to 1-OH-ibuprofen and carboxyl-ibuprofen, respectively. PI also can be hydrolyzed to release ibuprofen, which can generate 2-OH-ibuprofen, carboxyl-ibuprofen, and ibuprofen glucuronide. After a single oral administration (400 mg/kg) of PI, ibuprofen and ibuprofen glucuronide are the main plasma metabolites of PI; they have, respectively, C max of 530 and 215 M, T max of 1 and 2 h, elimination t 1/2 of 7.7 and 5.3 h, and area under the concentration-time curve (0 -24 h) of 1816 and 832 M ϫ h. Intact PI was detected in several tissues but not in plasma; at a higher PI dose (1200 mg/kg), PI plasma levels were 12.4 M. PI generated the same metabolites in mouse plasma as conventional ibuprofen, but with much lower levels, perhaps accounting for the enhanced safety of PI. The antitumor effect of PI was significantly associated with plasma ibuprofen levels (p ϭ 0.016) but not with xenograft ibuprofen levels (p ϭ 0.08), suggesting a complex anticancer effect. These results provide a pharmacological basis to explain, at least in part, the anticancer efficacy and safety of this promising compound and indicate that PI merits further evaluation as an anticancer agent.

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Section: Introductionmentioning

confidence: 99%

Phospho-Ibuprofen (MDC-917) Is a Novel Agent against Colon Cancer: Efficacy, Metabolism, and Pharmacokinetics in Mouse Models

Xie¹,

Sun²,

Tang³

et al. 2011

J Pharmacol Exp Ther

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“…[1][2][3][4][5][6][7][8][9] Our case illustrates that ibuprofen may cause significant toxicity in children. The wide availability of this over-thecounter product in pediatric formulations makes this a particular concern in children.…”

Section: Discussionmentioning

confidence: 99%

“…Based on these and additional data from adult overdoses, an ibuprofen nomogram was proposed. McElwee et al 8 prospectively studied 329 cases of ibuprofen overdose that included 135 pediatric cases. The majority of patients in this study were managed at home without adverse outcome.…”

Section: Discussionmentioning

confidence: 99%

Serious Toxicity in a Young Child Due to Ibuprofen

Oker

Hermann

Baum

et al. 2000

Academic Emergency Medicine

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Abstract. An 18-month-old male presented to the emergency department (ED) for evaluation of lethargy and apnea. Four hours before presentation, the patient was found with an empty bottle of ibuprofen, an ingestion of as much as 7.2 grams (600 mg/kg). The ED course was remarkable for a 30-second tonic-clonic seizure. Laboratory analysis was notable for metabolic acidosis. Four-hour and 7.5-hour serum ibuprofen levels were 640 and 39 g/mL, respectively. Following treatment, the patient improved and was extubated the next morning. While metabolic acidosis has been frequently described at doses exceeding 400 mg/kg, seizures occurring early in the course of ibuprofen toxicity have been rarely noted. Key words: ibuprofen; poisoning; pediatrics. ACADEMIC EMERGENCY MEDICINE 2000; 7:821-823 Ibuprofen is a commonly used overthe-counter nonsteroidal anti-inflammatory analgesic derived from propionic acid. In general, overdoses of ibuprofen result in mild effects. These effects include abdominal pain, nausea, vomiting, lethargy, headache, tinnitus, and ataxia.1 Serious toxicity, including coma, apnea, metabolic acidosis, hypotension, bradycardia, and renal and hepatic dysfunction, has been observed in ingestions of more than 400 mg/kg. Symptoms usually develop within four hours of ingestion. CASE REPORTAn 18-month-old, 12-kg male with an unremarkable past medical history was brought to the emergency department (ED) for evaluation of lethargy. According to the parents, the patient was found approximately four hours prior to presentation with an empty bottle of ibuprofen, and with pill fragments in his mouth. The patient had two episodes of emesis; one spontaneous and the other manually induced by a grandparent. After a brief period of relatively normal behavior, the parents noted that the patient became limp and was not easily aroused. The patient subsequently became apneic, prompting the parents to bring him to the ED. The patient's past medical history included eczema and otitis media. His parents indicated that he was occasionally given pseudoephedrine but was not given any in the last 24 hours. Further, it was discovered that his grandmother took lisinopril, for which all tablets were accounted.Later investigation indicated a potential ingestion of as much as 7.2 grams of ibuprofen (600 mg/kg).On presentation to the ED, the patient was lethargic. Vital signs were temperature (rectal) 96.8ЊF, respiratory rate 16 breaths/min, heart rate 123 beats/min, and blood pressure 118/48 mm Hg. The patient's vital signs remained in this range throughout his ED course. Physical exam was significant for an intact gag reflex, reactive pupils (3 mm), and withdrawal from painful stimuli. He received, in increments, a total of 600 mL of normal saline and 1 mg of naloxone without response. A short time later the patient sustained a 30-second tonicclonic seizure, which resolved with lorazepam 1 mg IV push. The patient then became apneic, requiring endotracheal intubation. Subsequent lavage with a 12-Fr nasogastric tube and 300 mL of norm...

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“…One child was noted to develop a metabolic acidosis, lethargy, and apnea after an ingestion of 666 mg/kg. A subsequent retrospective review of 329 cases [43] reported that 42 % of patients developed GI upset as the primary adverse event, with 30 % of patients exhibiting CNS depression with only one of these patients experiencing severe symptoms attributable to ibuprofen. Fatalities following ibuprofen overdose often are associated with significant hypotension [31,44], metabolic acidosis [31,44], oliguria [30], coma [31,44], and multiple organ system failure [31].…”

Section: Case Continuedmentioning

confidence: 99%

Case Files of the University of California, San Francisco Medical Toxicology Fellowship: Seizures and a Persistent Anion Gap Metabolic Acidosis

Arens

Smollin

2016

J. Med. Toxicol.

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A 17-year-old female was brought into the emergency department (ED) by ambulance after being found unresponsive by her parents at home. She was last seen normal 4 hours previously, and a text message sent to her boyfriend indicated her intention to overdose on ondansetron and loratadine. Upon arrival of emergency medical services, she was administered naloxone without effect, and supportive measures including bag valve mask ventilation were initiated. En route to the ED, she had a witnessed generalized tonic-clonic seizure, and she was treated with midazolam.In the ED, the patient's vital signs were BP 125/53 mmHg, HR 130/min, RR 18/min, and temperature 33.9°C (rectal). Her physical exam was notable only for a Glasgow Coma Scale (GCS) of 3 without a gag reflex. Her pupil size was not commented upon, and she was immediately intubated for airway protection.

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A prospective, population-based study of acute ibuprofen overdose: Complications are rare and routine serum levels not warranted

Cited by 51 publications

References 7 publications

Phospho-Ibuprofen (MDC-917) Is a Novel Agent against Colon Cancer: Efficacy, Metabolism, and Pharmacokinetics in Mouse Models

Phospho-Ibuprofen (MDC-917) Is a Novel Agent against Colon Cancer: Efficacy, Metabolism, and Pharmacokinetics in Mouse Models

Serious Toxicity in a Young Child Due to Ibuprofen

Case Files of the University of California, San Francisco Medical Toxicology Fellowship: Seizures and a Persistent Anion Gap Metabolic Acidosis

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