Yao Xue Xue Bao. 2003 Jun;38(6):412-5.
[Stereoselectivity in biliary excretion of trans tramadol and trans O-demethyltramadol in rats]

[Article in Chinese]

Liu HC, Yu Y, Wang N, Hou YN, Wang YL.

Department of Pharmacology, Hebei Medical University, Department of Clinical Pharmacology, Bethune International Peace Hospital, Shijiazhuang, China.

AIM: To investigate the stereoselectivity in biliary excretion of trans tramadol (trans T) and trans O-demethyltramadol (M1) in rats. METHODS: After a single intravenous dose of trans T hydrochloride (10 mg.kg-1) or M1 (2.5 mg.kg-1) to rats, the bile was collected for 30 min, then, blood was obtained from the heart. The enantiomers of trans T, M1 and M1 conjugated with glucuronic acid (M1c) in the bile and plasma were analyzed by high performance capillary electrophoresis (HPCE). RESULTS: After the rats were given trans T, the bile concentrations of (+)-trans T were higher than those of (-)-trans T, and the (+)/(-)-trans T ratios were lower compared with those in the plasma. After the rats were given M1, the bile concentrations of (+)-M1 were higher than those of (-)-M1, and the bile concentrations of (+)-M1c were lower than those of (-)-M1c. The glucuronidation rate of (+)-M1 was lower than that of (-)-M1 in the bile. CONCLUSION: The biliary excretion of trans T and M1 was stereoselective, (+)-trans T and (-)-M1 being preferentially excreted.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14513798&dopt=Abstract tramadol Ultram [PubMed - in process]

atauni.edu.tr

Tramadol is an important spinal drug which produces analgesia following intrathecal injection. It is well known that fatty acids (FAs) play an important role in membrane fluidity of the blood-brain barrier (BBB) tissue, which blocks and/or controls the transportation of toxic substances into the brain. The aim of this study was to investigate the effect of a spinal drug (tramadol) on the concentrations and compositions of fatty acid in BBB tissues of New Zealand male rabbits. The total cellular fatty acid profiles of the tissues in three spinal cord sections (cervical, thoracal and lumbar) and in the brain of rabbits with or without drug administration were determined by gas chromatography using Sherlock Microbial Identification System (MIS) software (Microbial ID, Newark, DE, U.S.A.) with a database of FAME profiles for eukary. The relative percentage of the fatty acid methyl ester (FAME), 24 : 1 omega9c nervonic and 17 : 1 omega8c, did not change with tramadol treatments. However, there was an increase in the concentration of the FA 16 : 0, 18 : 1 omega7c DMA, 18 : 1 omega9c, sum in future 4, sum in future 8, sum in future 9, 18 : 0, 20 : 4 omega6c, sum in future 14, 22 : 4 omega6c, in contrast to a decrease in the percentages of the following FAMEs; 20 : 0, 20 : 1 omega9c. In the brain, there was an increase in the concentration of the FA 18 : 1 omega9c, sum in future 8 and 18 : 0, in contrast to a decrease in the percentages of two FAMEs, 16 : 0, 20 : 4 omega6c and 22 : 6 omega3c. The number of fatty acids were 20 in the spinal cord sections and 8 in the brain tissues of control animals compared to 15-18 fatty acids in the spinal cord section and 7 in the brain tissues of drug administered animals. The overall changes in the concentrations and numbers of FAs suggest that the spinal drug tested in this study has a side effect of disrupting of membrane fluidity of the BBB, which may cause neurotoxicity.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14519944&dopt=Abstract tramadol Ultram




Eur J Drug Metab Pharmacokinet. 2003 Jul-Sep;28(3):223-32.
Metabolic assessment in liver microsomes by Co-activating cytochrome P450s and UDP-glycosyltransferases.

Yan Z, Caldwell GW.

Division of Drug Discovery, Johson & Johnson Pharmaceutical Research & Development, LLC, Spring House PA 19477, USA.

A "dual-activity" microsomal system in which both CYPs and UGTs were active was evaluated for studies of metabolic stability and in-vitro metabolite profiling. In this "dual-activity" system, alamethicin, a pore-forming peptide, was used to activate UGTs in human liver microsomes without affecting CYP activity. Interference studies indicated that CYP cofactors had little effect on UGT surrogate activity as measured by glucuronidation of acetaminophen and trifluoperazine. Further, UGT cofactor, UDPGA (< 2 mM), did not inhibit the marker activity of five major CYPs including 1A2, 2C9, 2C19, 2D6 and 3A4, suggesting that both oxidation and glucuronidation can be co-activated in microsomes. In a comparison study, compounds with significant glucuronidation showed distinct stability profiles in the "dual-activity" system, compared to the conventional microsomal incubation in which only CYPs were active. For compounds with minor or no glucuronidation, the metabolic stability remained similar between the "dual-activity" system and the conventional microsomal incubation. The feasibility of this "dual-activity" system utilized for metabolite profiling was also investigated using tramadol as a model drug. It was found that oxidative metabolites of tramadol generated in the "dual-activity" system matched those detected in the conventional microsomal incubation. However, tramadol glucuronide was observed in the "dual-activity" system but not in the conventional micromosal incubation. Results clearly suggest that the "dual-activity" system is a valuable in vitro model for metabolism studies in drug discovery.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14527096&dopt=Abstract tramadol Ultram [PubMed - in process]




Arq Gastroenterol. 2004 Jan-Mar;40(1):35-9. Epub 2003 Oct 06.
Stapled hemorrhoidectomy for the treatment of hemorrhoids.

Nahas SC, Borba MR, Brochado MC, Marques CF, Nahas CS, Miotto-Neto B.

Hospital S rio Liban s.

BACKGROUND: The use of circular staplers in the treatment of hemorrhoidal disease is known as a simple procedure, with low morbidity, less post-treatment pain and with the same efficacy when compared to the classical hemorrhoidectomy. AIM: Analyze the operative technique, intra-operative and immediate postoperative complications and late results in 100 patients treated for hemorrhoid disease by stapling technique. PATIENTS AND METHODS: The group included 53 males and 47 females with mean age of 49.8 years, operated during the period June 2000 to June 2002 in the "Hospital Universit rio" (S o Paulo University Hospital) and "Hospital S rio Liban s", in S o Paulo, SP, Brazil. RESULTS: The majority of patients (78%) were discharged on the first post-operative day. Eight patients required supplementary analgesia and were given intramuscular diclofenac sodium and four of them received intramuscular tramadol. One intraoperative complication was bleeding which was difficult to control and required a blood transfusion. One patient was reoperated on the first postoperative day due to intermittent and persistent bleeding, however without hemodynamic changes or a drop in hematocrit. Two patients presented hemorrhoidal thrombosis in the early postoperative stage. The postoperative follow-up displayed: recurrence of prolapse, five cases (5%); anal sub-stenosis, two cases (2%); anal fissure, one case (1%); persistent pain, two cases (2%). Seven reoperations were performed: one due to bleeding, one due to sub-stenosis and five due to recurrence of hemorrhoidal prolapse and persistence of symptoms. CONCLUSIONS: Stapling is simple to accomplish, has low postoperative pain and rate of complications, however, the incidence of late reoperations is rather high and therefore major follow-up for better analysis is required.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14534663&dopt=Abstract tramadol Ultram [PubMed - in process]

BANYAN.ummed.edu

When patients with acute porphyrias are treated with antihypertensives and analgesics, they could be placed at increased risk of developing porphyric attacks, since little is known about the potential for many of these drugs to induce these attacks. We used primary chick embryo liver cells, which maintain intact heme synthesis and regulation, to study the effects of antihypertensives and analgesics on porphyrin accumulation. Cells were treated with desferrioxamine to block heme synthesis partially, simulating conditions encountered in porphyric patients. Typically, cells were treated for 20 hr with the test drugs (3.16 to 1000 microM), along with desferrioxamine. Porphyrins were measured spectrofluorometrically, as uro-, copro,- and protoporphyrin. The evaluated drugs included six antihypertensives (two calcium channel blockers, an angiotensin receptor antagonist, and three inhibitors of angiotensin converting enzyme) and eight analgesics. Of the calcium channel blockers tested, nifedipine greatly increased porphyrin accumulation, whereas diltiazem caused only a slight increase. Losartan (an angiotensin receptor antagonist), captopril, or lisinopril (two angiotensin converting enzyme inhibitors) produced only small increases in porphyrin accumulation. In contrast, enalapril (another angiotensin converting enzyme inhibitor) substantially increased porphyrin accumulation when given in high concentrations. Among the analgesics tested, fentanyl and tramadol produced the highest porphyrin accumulations. Nalbuphine, hydrocodone, oxycodone, and dezocine were moderately or weakly porphyrogenic, whereas buprenorphine and morphine did not increase porphyrin accumulation. These studies suggest that patients with acute porphyrias may be at greater risk for developing porphyric attacks when treated with nifedipine (compared with diltiazem), enalapril (compared with captopril or lisinopril), and tramadol (compared with the other analgesics).

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10449201&dopt=Abstract tramadol Ultram