Tramadol drug is used for pain relief
Tramadol (generic for Ultram) is a prescription medication used for the management of moderate to moderately severe pain. Tramadol® has been prescribed to more than 55 million patients worldwide; Ultram® has been prescribed to more than 21 million patients in the U.S.

Population pharmacokinetic modelling of tramadol with application of the NPEM algorithms.

Gan SH, Ismail R, Wan Adnan WA, Zulmi W, Jelliffe RW.

Department of Pharmacology, School of Medical Science, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. usmpcrprob@yahoo.com

BACKGROUND AND OBJECTIVE: Although the kinetic behaviour of tramadol has been described, the present study is the first to our knowledge, to report specifically on the population pharmacokinetic modelling of tramadol hydrochloride. METHODS: The parametric Iterative Two-stage Bayesian Population Model (IT2B) program followed by the Non-parametric Expectation Maximization Population Model (NPEM2) program was used to determine population pharmacokinetic parameter values of tramadol in 138 postoperative orthopaedic Malaysian patients. All patients had received a 100 mg intravenous dose of tramadol, infused over 2-3 min, as their first postoperative analgesic. Blood was sampled at 0 min and subsequently at 15, 30 min, 1, 2, 4, 8, 16, 20 and 24 h for serum tramadol high-performance liquid chromatography analysis. RESULTS AND DISCUSSION: The one-compartmental model pharmacokinetic parameters--volume of distribution (Vd), elimination rate constant (kel) and the total clearance rates (ClT)--found were: mean Vd = 167.6 +/- 63.84 L; median Vd = 161.48 L; mean kel = 0.1241 +/- 0.056 h(-1); median kel = 0.1138 h(-1); ClT = 19.57 +/- 9.51 L/h; median ClT =18.12 L/h. The interindividual coefficient of variation of ClT (48.56%) was higher than that of Vd (38.09%), indicating the presence of other possible influencing factors on tramadol's ClT such as CYP2D6 polymorphism, gender and age. Overall, NPEM2 suggested more diversity in the population than did IT2B.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15482390&query_hl=2

Immediate postoperative pain management in patients undergoing major abdominal surgery after remifentanil-based anesthesia: sufentanil vs tramadol.

[Article in English, Italian]

Cafiero T, Di Minno RM, Sivolella G, Di Iorio C.

Department of Anesthesia, Postoperative Intensive Care, Burn Center and Hyperbaric Center A. Cardarelli Hospital, Naples, Italy. tcafiero@tiscali.it

AIM: The transition from intraoperative analgesia to postoperative analgesia must be planned carefully after remifentanil-based anesthesia, due to the short duration of action of remifentanil. The aim of this study is to compare the efficacy and safety of 2 transition strategies using sufentanil or tramadol for early postoperative pain relief in patients who had major abdominal surgery under general anesthesia with remifentanil/sevoflurane. METHODS: Sixty patients participated in this double-blind, prospective study and were randomly assigned to either sufentanil (S) group or tramadol (T) group. Twenty minutes before the end of surgery the patients received either a bolus of 0.15 microg kg(-1) sufentanil (group S) or tramadol 100 mg (group T). Mean arterial pressure (MAP), heart rate (HR) and rate pressure product (RPP=systolic arterial pressure (SAP)xHR), analgesia by a verbal rating score (VRS) and sedation by a sedation score (SS) were evaluated at emergence from anesthesia. RESULTS: A statistically significant difference in HR between the 2 groups was recorded at extubation (78+/-13 in group S vs 86+/-24 in group T). A significant decrease of RPP values at extubation and 5 minutes later were found in group S in comparison with group T. VRS values were significantly lower in sufentanil group at 5 and 10 minutes after awakening. CONCLUSIONS: Sufentanil provided more effective transition analgesia in comparison with tramadol. The effects of remifentanil dissipated rapidly and analgesia with major opioids was required. A bolus dose of sufentanil 0.15 microg kg(-1) was efficacious in controlling the hemodynamic parameters at awakening from anesthesia. The lower HR values and, consequently the lower RPP values are of utmost importance especially in the aged cardiovascular risk patient.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15467498&query_hl=2

Long-term exposure of rats to tramadol alters brain dopamine and alpha 1-adrenoceptor function that may be related to antidepressant potency.

Faron-Gorecka A, Kusmider M, Inan SY, Siwanowicz J, Piwowarczyk T, Dziedzicka-Wasylewska M.

Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.

The aim of the present study was to determine whether tramadol, which has a potential antidepressant efficacy, evokes, when administered repeatedly, changes similar to the alterations induced by conventional antidepressant drugs. Repeated administration of tramadol (20 mg/kg i.p. for 21 days) enhanced the d-amphetamine-induced locomotor hyperactivity and increased the density of alpha(1)-adrenoceptors in the rat brain cortex, as measured by saturation analysis of [(3)H]prazosin binding. Autoradiographic analysis of [(3)H]7-OH-DPAT and [(3)H]raclopride binding revealed a significant up-regulation of dopamine D2 and D3 receptors in the rat nucleus accumbens upon repeated treatment with tramadol. All the above-mentioned effects induced by repeated administration of tramadol resemble the effects induced by conventional antidepressants. However, tramadol when administered repeatedly did not increase the levels of mRNA encoding for brain-derived neurotrophic factor (BDNF) and its receptor, TrkB. This is what differs tramadol from conventional antidepressants, since neurotrophic effects of these drugs have recently been postulated.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15464068&query_hl=2

Tramadol (Ultram) concentrations in death investigation and impaired driving cases and their significance.

Clarkson JE, Lacy JM, Fligner CL, Thiersch N, Howard J, Harruff RC, Logan BK.

Washington State Toxicology Laboratory, Forensic Laboratory Services Bureau, Washington State Patrol, 2203 Airport Way South, Seattle, WA 98134, USA. Jayne.Clarkson@wsp.wa.gov

We reviewed a series of 66 deaths in Washington State between 1995-2000 in which tramadol (Ultram and Ultracet, Ortho-McNeil) was detected in the decedent's blood, in order to assess the role tramadol was determined to have played. Additionally, we reviewed a series of 83 impaired driving cases in which tramadol was detected in order to establish a non-lethal blood tramadol concentration reference range. In both populations, tramadol was consistently found together with other analgesic, muscle relaxant, and CNS depressant drugs. Death was rarely attributable to tramadol alone. However, tramadol may be a significant contributor to lethal intoxication when taken in excess with other drugs, via the potential interaction with serotonergic antidepressant medications, as well as the potential for increased CNS depression. Although the incidence of tramadol detection has increased consistently over the last eight years, there is no evidence of a corresponding increase in the number of cases in which death was attributed solely to tramadol. Blood drug concentrations in many deaths exceeded the therapeutic serum range of 0.28-0.61 mg/L; however, the concentrations overlapped almost completely with the range identified in living subjects arrested for impaired driving. These findings suggest caution in the interpretation of blood tramadol concentrations outside of the recognized therapeutic range. It also suggests that the drug, even when used in moderate excess, is not a principle cause of death in suicidal or accidental deaths.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15461118&query_hl=2

Impact of mailed warning to prescribers on the co-prescription of tramadol and antidepressants.

Shatin D, Gardner JS, Stergachis A, Blough D, Graham D.

Center for Health Care Policy and Evaluation, UnitedHealth Group, Minneapolis, MN 55344, USA. Deborah_shatin@uhc.com

PURPOSE: An evaluation was made of the effectiveness in changing prescribing behavior of 'Dear Health Professional (DHP)' letters mailed by the manufacturer to physicians and other health professionals advising them of safety information on co-prescribing of tramadol and antidepressants. METHODS: A retrospective cohort analysis of prescription claims of all plan members from 12 UnitedHealth Group-affiliated health plans who received a first prescription for tramadol between 1 April 1995 and 31 December 1996. The prevalence of co-prescribing of antidepressants and tramadol relative to the date of the 'DHP' communication was determined. RESULTS: 9218 plan members received an initial prescription for tramadol within the observation period. Prior to the date of the 'DHP' communication 1061/4774 (22.2%) members received a prescription for an antidepressant within 30 days of their first prescription for tramadol. Following the date of the communication 844/4444 (19.0%) of members received an antidepressant within 30 days of their first prescription for tramadol. An overall decreasing linear trend in antidepressant co-prescribing was evident over the observation period, but there was no statistically significant acceleration in the decrease following this communication. CONCLUSIONS: The mailed 'DHP' advisory letter did not affect the rate of co-prescribing of tramadol with antidepressants.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15386714&query_hl=2

Quality assessment for tramadol in pharmaceutical preparations with thin layer chromatography and densitometry.

Krzek J, Starek M.

Jagiellonian University, Collegium Medicum, Department of Inorganic and Analytical Chemistry, 9 Medyczna Str., 30-688 Krakow, Poland. jankrzek@cm-uj.krakow.pl

Research studies have been carried out to develop a chromatographic and densitometric method suitable for identification and determination of tramadol and impurities. In addition, the stability of tramadol in solutions was investigated, including an effect of solution pH, temperature and incubation time. In the first instance the conditions for identification and quantitative determination of tramadol and impurities in pharmaceutical preparations were established. The separation was performed on silica gel-coated chromatographic plates (HPTLC) using two mobile phases: (I) chloroform-methanol-glacial acetic acid (9:2:0.1, v/v/v); (II) chloroform-toluene-ethanol (9:8:1, v/v/v). The UV densitometry was carried out at lambda = 270 nm. The developed method is of high sensitivity and low detection and determination limits ranging from 0.044 to 0.35 microg. For individual constituents the recovery ranges from 93.23 to 99.66%. The next step was to evaluate the stability of tramadol and determine a method of decomposition under various experimental conditions. It was found that tramadol decomposes in various ways in acidic and basic environments producing (1RS)-[2-(3-methoxyphenyl)cyclohex-2-enyl]-N,N-dimethylmethanamine (imp. B) and (1RS, 2RS)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol (imp. cis-T) or imp. cis-T, respectively.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15386511&query_hl=2

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