AAPS PharmSciTech. 2002;3(3):E27.
Influence of complex solubility on formulations based on lambda carrageenan and basic drugs.

Aguzzi C, Bonferoni MC, Fortich MR, Rossi S, Ferrari F, Caramella C.

Department of Pharmaceutical Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.

The purpose of the present work was to compare the behavior of some drug/carrageenan complexes having different solubility in water, in a controlled release formulation. Diltiazem HCl, bupropion HCl, metoprolol tartrate, and tramadol HCl were used as model drugs. The complexes were characterized by means of solubility measurements, release test at constant surface area, and water uptake measurements, and the results were related to their performance in controlled release formulations. For the more soluble complexes (involving metoprolol and tramadol) the occurrence of gelation after hydration was observed, while diltiazem complex apparently did not gellify; bupropion behavior was intermediate. A correspondence was found between the observed differences in complex solubility and hydration-gelation behavior and the drug release profiles. For all the drugs considered, the release was completed in about 10 to 12 hours, but different kinetics were observed depending on the solubility of the complexes. All the considered complexes seem suitable for controlled release purposes, although the data obtained show the relevance of the complex solubility to drug release profiles.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12916942&dopt=Abstract tramadol Ultram

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We have used the sucrose gap method to measure the effects of drugs on the electrophysiological properties of rat sciatic nerves. The results showed that 4-aminopyridine produced a slight conduction block, prolonged the duration of action potential, enhanced the hyperpolarizing afterpotential, and elicited a hump that followed the action potential. In the presence of 4-aminopyridine, the impulse-blocking activity of lidocaine and tramadol was enhanced. Both lidocaine and tramadol effectively depressed the delayed depolarization generated by 4-aminopyridine. While tramadol decreased the activity-evoked hyperpolarizing afterpotentials, lidocaine completely removed them. These findings indicate that lidocaine may be more effective in blocking the Na(+) channels than tramadol. Tramadol may be more effective on the delayed rectifier K(+) channels than lidocaine. Copyright 2003 S. Karger AG, Basel

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12928579&dopt=Abstract tramadol Ultram




Eur J Pain. 2003;7(5):439-48.
Interaction between metamizol and tramadol in a model of acute visceral pain in rats.

Poveda R, Planas E, Pol O, Romero A, Sanchez S, Puig MM.

Department of Pharmacology, School of Odontology, University of Barcelona, Barcelona 08807, Spain.

Tramadol (TRM) and metamizol (MTZ) are drugs with complex mechanisms of action, extensively used in combination in pain management. In the present investigation we have evaluated the interaction between MTZ:TRM in the ethacrinic acid writhing test in rats. Dose-response curves (s.c.) were obtained for each drug individually, combined in fixed potency ratios (1:0.3, 1:1, 1:3), and for MTZ in presence of a fixed-dose of TRM (3.5 mg/kg). Interactions were analysed using isobolograms, interaction indexes (INT-I) and ANOVA. We used naloxone (1 mg/kg s.c.) to determine the opioid-component of the effects (ED80). Isobolograms demonstrated antagonism at the ED20, for 1:0.3 and 1:3 mixtures (p<0.01), whereas 1:1 was additive. At the ED50 and ED80 all combinations showed synergy. Fixed-dose experiments demonstrated that treatment (p<0.0001), dose (p<0.0001), and their interaction (p<0.0001) were statistically significant. Naloxone partially antagonized TRM (67%), but not MTZ; the percentage reversal of the combinations was directly related to the dose of TRM in the combination. The results show that the MTZ:TRM interaction on antinociception is synergistic or antagonistic depending on the level of effect. Synergy is demonstrated at 50% or higher levels, thus supporting the results obtained in humans by our group. Below the ED50 antagonism or additivity is present depending on the ratio of the combination. The mechanisms of the interaction remain unknown.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12935796&dopt=Abstract tramadol Ultram

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We compared the antiemetic efficacy of tropisetron versus droperidol in women given tramadol after total hysterectomy. Forty patients were randomly allocated to group 1 (n = 20, tropisetron 0.05 mg/kg intravenously) or group 2 (n = 20, droperidol 15 micrograms/kg intravenously). Tramadol infusion (intravenously), for post-operative analgesia, was started at fascia closure. Incidences of post-operative nausea and vomiting, pain intensity, tramadol use, and the need for a rescue antiemetic (metoclopramide 10 mg) were recorded 0 h, 2 h, 6 h, 12 h, 24 h and 48 h post-operatively. Vomiting and nausea incidences were reported fewer in group 1 than in group 2, but statistical significance was only reached for vomiting incidence 6 h post-operation. Tropisetron seems to have better antiemetic properties than droperidol in patients receiving tramadol because of the length of its duration of action. Further studies, investigating alternative ways of managing post-operative nausea and vomiting, and the use of tramadol for post-operative analgesia, are needed.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12964501&dopt=Abstract tramadol Ultram [PubMed - in process]

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A successful heterotopic cardiac transplantation was performed between sibling female Yorkshire Juvenile swine. Adequate pre-medication with azaperone and a smooth induction were ensured for both pigs, which were anaesthetized simultaneously with sodium thiopentone followed by endotracheal intubation and intermittent positive pressure ventilation. Inhalation anaesthetic agents were used for maintenance, neuromuscular blockade was achieved with cisatracurium and both fentanyl and tramadol were used to provide analgesia. Invasive monitoring was used in both the donor and recipient. Central venous pressure (CVP) was maintained at > 10 cm H2O and mean arterial pressure (MAP) > 60 mmHg. Heparin was injected during the surgical dissection of the heart in the donor to prevent coronary thrombosis and prior to aortic side clamping for end-to-side anastomosis of the donor heart in the recipient abdomen. After transplantation, the cardiovascular parameters of the recipient showed a MAP of 85-105 mmHg and a CVP of 8-10 cm H2O while echocardiography of the transplanted heart confirmed an ejection fraction (EF) of 80%. A functional anaesthetic team was assembled and trained to provide anaesthesia for porcine cardiac transplantation. The transplanted heart suffered pump failure after 69 days and was excised for performance of tissue analysis.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12974058&dopt=Abstract tramadol Ultram