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Pharmaceutical residues in the river Rhine-results of a one-decade monitoring programme.
J Environ Monit. 2008 May; 10(5): 664-70
Sacher F, Ehmann M, Gabriel S, Graf C, Brauch HJ
In this paper, results of an extensive monitoring programme for pharmaceutical residues in the river Rhine are presented. For one decade (1997 until 2006), the occurrence of widely used human pharmaceuticals like analgesics, lipid regulators, antiepileptics and others has been studied at four locations along the river Rhine. The results of more than 500 analyses clearly prove that compounds such as carbamazepine or diclofenac are regularly found in the river Rhine in concentrations up to several hundred ng per litre. Combining concentration levels with data on water flow enables the calculation of transports, which e.g. for carbamazepine or diclofenac were in the range of several tons per year. The evaluation of the long-term monitoring data shows that only a slight decrease in concentration levels as well as in annual transports can be observed and thus the contamination of the river Rhine by pharmaceutical residues during the last decade has to be regarded as almost constant. Seasonal variations can be detected for bezafibrate, diclofenac and ibuprofen, for which the concentrations are much lower in the summer months. A more effective removal during wastewater treatment in the warmer periods of the year seems to be the major reason for those variations. For carbamazepine, no comparable seasonal effect can be found.
Spine. 2008 May 1; 33(10): 1119-24
Sucato DJ, Lovejoy JF, Agrawal S, Elerson E, Nelson T, McClung A
STUDY DESIGN: A retrospective review comparing patients who had postoperative ketorolac and those who did not following posterior spinal fusion and instrumentation (PSFI) for adolescent idiopathic scoliosis (AIS). OBJECTIVE: To analyze the effect of postoperative ketorolac on the incidence of pseudoarthrosis in postoperative AIS patients. SUMMARY OF BACKGROUND DATA: Ketorolac (Toradol, Roche Laboratories, Nutley, NJ) is a nonsteroidal antiinflammatory drug that is an effective adjunct to manage postoperative pain. It has been previously demonstrated to inhibit spinal fusion in adult patients undergoing a L4 to sacral fusion. To our knowledge, there are no large studies analyzing this effect following PSFI for AIS. METHODS: An IRB-approved retrospective medical record review was performed from 1994 to 2000 of patients undergoing a PSFI for AIS at a single institution. Segmental spinal instrumentation (Texas Scottish Rite Hospital) and iliac crest bone graft were used in both groups. Demographic and operative data were recorded. Patients were divided into those who had postoperative ketorolac (K group) and those who did not (NK group). Patients who had a surgically confirmed pseudoarthrosis were identified and the K group and NK group were statistically compared. RESULTS: There were 161 patients in the NK group and 158 in the K group. There were no differences with respect to age (14.4 vs. 14.2 years), gender (83.9% vs. 84.8% females), levels fused (9.8 vs. 9.7), or preoperative curve magnitude (57.9 degrees vs. 58.9 degrees ). In the K group, the number of doses of ketorolac administered was 6.7 for an average of 26.7 mg for a duration of 46 hours after surgery. Patients in the K group were more likely to have Motrin (average 5.8 doses) compared with the NK group (average 0.7 doses) (P < 0.01). No patient in the K group had a history of cigarette smoking compared with 2 patients in the NK group, both of whom went on to solid arthrodesis. The overall incidence of pseudoarthrosis was 2.5% for all patients. There was no difference in the incidence of pseudoarthrosis comparing the K (1.9%) and the NK group (3.1%)(P = 0.7). When the single rod posterior implants were excluded, there was no difference between the K (0.7%) and NK groups (1.8%) (P = 0.58). CONCLUSION: Ketorolac does not increase the incidence of developing a pseudoarthrosis when used as an adjunct for postoperative analgesia following a PSFI for AIS using segmental spinal instrumentation and iliac crest bone graft. The differences seen here compared with adults may be due to the greater healing potential in these young patients. We recommend utilization of ketorolac after surgery to supplement pain management when necessary.
Br J Anaesth. 2008 Apr 29;
Jokela R, Ahonen J, Tallgren M, Haanpää M, Korttila K
BACKGROUND: /st> Multimodal pain management has been suggested to improve postoperative analgesia. In this study, we evaluated the quality of analgesia in women undergoing day-case gynaecological laparoscopic surgery, after premedication with pregabalin 75 mg (P75) or 150 mg (P150), compared with diazepam 5 mg (D5). All patients were given ibuprofen 800 mg orally. METHODS: /st> Altogether 90 consenting women were anaesthetized in a standardized fashion. Postoperative analgesia was provided by ibuprofen 800 mg twice a day with fentanyl i.v. on request in the recovery room (RR), and combination tablets with acetaminophen and codeine after the RR. The visual analogue scale (VAS) scores for pain and side-effects and the amounts of postoperative analgesics were recorded for 24 h after surgery. The areas under the curves (AUC) were calculated for the VAS scores for pain at rest, pain in motion, and pain at cough 1-8 and 1-24 h after surgery. RESULTS: /st> The median AUC values for VAS scores for pain at rest (P=0.048) and in motion (P=0.046) 1-8 h after surgery were lower in the P150 group than that in the D5 group. The amounts of rescue analgesics or the degree of drowsiness did not differ in the three study groups. CONCLUSIONS: /st> Analgesia was better after premedication with pregabalin 150 mg than after diazepam 5 mg, both with ibuprofen 800 mg, during the early recovery after day-case gynaecological laparoscopic surgery. Pregabalin 150 mg did not reduce the amount of postoperative analgesics required.
Sodium-coupled Monocarboxylate Transporters in Normal Tissues and in Cancer.
AAPS J. 2008; 10(1): 193-9
Ganapathy V, Thangaraju M, Gopal E, Martin PM, Itagaki S, Miyauchi S, Prasad PD
SLC5A8 and SLC5A12 are sodium-coupled monocarboxylate transporters (SMCTs), the former being a high-affinity type and the latter a low-affinity type. Both transport a variety of monocarboxylates in a Na(+)-coupled manner. They are expressed in the gastrointestinal tract, kidney, thyroid, brain, and retina. SLC5A8 is localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to neurons and the retinal pigment epithelium. The physiologic functions of SLC5A8 include absorption of short-chain fatty acids in the colon and small intestine, reabsorption of lactate and pyruvate in the kidney, and cellular uptake of lactate and ketone bodies in neurons. It also transports the B-complex vitamin nicotinate. SLC5A12 is also localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to astrocytes and Müller cells. SLC5A8 also functions as a tumor suppressor; its expression is silenced in tumors of colon, thyroid, stomach, kidney, and brain. The tumor-suppressive function is related to its ability to mediate concentrative uptake of butyrate, propionate, and pyruvate, all of which are inhibitors of histone deacetylases. SLC5A8 can also transport a variety of pharmacologically relevant monocarboxylates, including salicylates, benzoate, and gamma-hydroxybutyrate. Non-steroidal anti-inflammatory drugs such as ibuprofen, ketoprofen, and fenoprofen, also interact with SLC5A8. These drugs are not transportable substrates for SLC5A8, but instead function as blockers of the transporter. Relatively less is known on the role of SLC5A12 in drug transport.
Oral-ibuprofen-induced acute renal failure in a preterm infant.
Pediatr Nephrol. 2008 Apr 30;
Erdeve O, Sarici SU, Sari E, Gok F
The side effects of indomethacin for ductal closure in preterm neonates (e.g. increased incidence of necrotizing enterocolitis, decreased cerebral blood volume and transient renal failure) have led clinicians to seek a safer alternative. Intravenous indomethacin and ibuprofen appear to be equally effective for patent ductus arteriosus closure, but oral ibuprofen remains an experimental option with theoretical advantages yet with potential side effects. We herein report a case of transient but severe acute renal failure developing in a preterm infant in whom oral ibuprofen was used and discuss the safety of this drug in relation to its pharmacokinetics.
Autism. 2008 May; 12(3): 293-307
Schultz ST, Klonoff-Cohen HS, Wingard DL, Akshoomoff NA, Macera CA, Ming Ji
The present study was performed to determine whether acetaminophen (paracetamol) use after the measles-mumps-rubella vaccination could be associated with autistic disorder. This case-control study used the results of an online parental survey conducted from 16 July 2005 to 30 January 2006, consisting of 83 children with autistic disorder and 80 control children. Acetaminophen use after measles-mumps-rubella vaccination was significantly associated with autistic disorder when considering children 5 years of age or less (OR 6.11, 95% CI 1.42-26.3), after limiting cases to children with regression in development (OR 3.97, 95% CI 1.11-14.3), and when considering only children who had post-vaccination sequelae (OR 8.23, 95% CI 1.56-43.3), adjusting for age, gender, mother's ethnicity, and the presence of illness concurrent with measles-mumps-rubella vaccination. Ibuprofen use after measles-mumps-rubella vaccination was not associated with autistic disorder. This preliminary study found that acetaminophen use after measles-mumps-rubella vaccination was associated with autistic disorder.
Osteoid Osteoma of a Cervical Vertebral Body.
Zentralbl Neurochir. 2008 Apr 29;
Radulovic DV, Slavik E, Rakic M
We report a very rare case of 5-year-old boy with osteoid osteoma of the cervical vertebral body. The patient presented with a 6-month history of neck pain with radiation into the shoulder and arm on the left side, which was relieved by ibuprofen. Neurological examination and plain radiographs of the cervical spine were normal. CT scan and bone scintigraphy, rather than MRI suggested the pathological diagnosis, which was confirmed on histological examination. The patient underwent excision of the lesion via an anterior approach with complete resolution of the pain postoperatively.
Chiral ionic liquids for enantioseparation of pharmaceutical products by capillary electrophoresis.
J Chromatogr A. 2008 Apr 12;
Tran CD, Mejac I
A chiral ionic liquid (IL), S-[3-(chloro-2-hydroxypropyl)trimethylammonium] [bis((trifluoromethyl)sulfonyl)amide] (S-[CHTA](+)[Tf(2)N](-)), which can be easily and readily synthesized in a one-step process from commercially available reagents, can be successfully used both as co-electrolyte and as a chiral selector for CE. A variety of pharmaceutical products including atenolol, propranolol, warfarin, indoprofen, ketoprofen, ibuprofen and flurbiprofen, can be successfully and baseline separated with the use of this IL as electrolyte. Interestingly, while S-[CHTA](+)[Tf(2)N](-) can also serve as a chiral selector, enantioseparation cannot be successfully achieved with S-[CHTA](+)[Tf(2)N](-) as the only chiral selector. In the case of ibuprofen, a second chiral selector, namely a chiral anion (sodium cholate), is needed for the chiral separation. For furbiprofen, in addition to S-[CHTA](+)[Tf(2)N](-) and sodium cholate, a third and neutral chiral selector, 1-S-octyl-beta-d-thioglucopyranoside (OTG), is also needed. Due to the fact that the chirality of this chiral IL resides on the cation (i.e., -[CHTA](+)), and that needed additional chiral selector(s) are either chiral anion (i.e., cholate) or chiral neutral compound (OTG), the results obtained seem to suggest that additional chiral selector(s) are needed to provide the three-point interactions needed for chiral separations.
Eur J Pharmacol. 2008 Apr 1;
Sorkin LS, Doom CM, Maruyama KP, Nanigian DB
Various animal models of pain are dependent on activation of different glutamate receptor subtypes. First degree burn of the paw elicits a secondary hyperalgesia that is dependent on Ca(2++) permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), but not N-methyl-d-aspartate (NMDA) receptors. The present study takes advantage of that specificity by examining the effects of spinal pretreatments of agents on this secondary hyperalgesia. Rats with indwelling intrathecal catheters were pretreated with agents prior to paw injury. Mechanical withdrawal thresholds were measured before, and for three h after the injury. Spinal pretreatment with cyclooxygenase (10 and 30 mug (S)-(+)-ibuprofen; and 3 and 30 mug ketorolac) and nitric oxide synthase (33 and 100 mug N(G) Nitro-l-arginine methyl ester hydrochloride (l-NAME) and 10 mug thiocitrulline) inhibitors resulted in no specific anti-allodynia. In contrast, ziconotide (0.3, 1.0 and 3 mug), the N-type voltage gated calcium channel antagonist was very effective in blocking burn-induced sensitivity at all doses used. l-type (Diltiazam 230 mug) and P-type (Agatoxin IVA 0.3 mug) calcium channel blockers produced intermediate effects. Thus, cyclooxygenase and nitric oxide synthase are assumed not to be downstream of Ca(2++) permeable AMPA receptors. Voltage gated calcium channels blockers could exert their effects either pre- or post-synaptically.
Nonaspirin NSAIDs, Cyclooxygenase 2 Inhibitors, and the Risk for Stroke.
Stroke. 2008 Apr 24;
Roumie CL, Mitchel EF, Kaltenbach L, Arbogast PG, Gideon P, Griffin MR
BACKGROUND AND PURPOSE: There is limited information regarding the cerebrovascular safety of cyclooxygenase 2 inhibitors (coxibs) and noncoxib nonsteroidal antiinflammatory drugs (NSAIDs). We determined whether specific NSAIDs, including coxibs, are associated with risk of stroke. METHODS: Retrospective cohort study among Tennessee Medicaid enrollees aged 50 to 84 years between January 1, 1999 and December 31, 2004. Noninstitutionalized persons with continuous enrollment in Medicaid and no stroke or other serious medical illness in the year before cohort entry were included. The 7 most common NSAIDs were examined: celecoxib, rofecoxib, valdecoxib, ibuprofen, naproxen, diclofenac, and indomethacin. Nonuse of NSAIDs was the reference group. Because new use is less susceptible to bias, we conducted a similar analysis confined to new users. The outcome was hospitalization for an incident cerebrovascular event: ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. RESULTS: The cohort included 336 906 persons, with 989 826 person-years of follow-up, and 4354 stroke hospitalizations. There were 4.51 strokes per 1000 person years in the nonuse group, 5.15 strokes per 1000 person years (adjusted HR 1.28, 95% CI 1.06, 1.53) with rofecoxib use, and 5.95 strokes per 1000 person years (adjusted HR 1.41, 95% CI 1.04, 1.91) with valdecoxib use. New use of rofecoxib and valdecoxib led to 6.06 (adjusted HR 1.46 95% CI 1.08, 1.98) and 6.19 (adjusted HR 1.39, 95% CI 0.74, 2.59) strokes per 1000 person years respectively. No other NSAID significantly increased the risk of incident stroke. CONCLUSIONS: Our results indicate an increased risk of stroke with current use of two highly selective coxibs, rofecoxib and valdecoxib, also shown to increase cardiovascular risk. These results also provide some reassurance about other specific NSAIDs regarding stroke risk.