Biomedical subjects

W Fleischer

Publications and source records attributed to W Fleischer.

At least 19 recordsLinked to original sources

PubMed2006

PVP-iodine in hydrosomes and hydrogel--a novel concept in wound therapy leads to enhanced epithelialization and reduced loss of skin grafts.

BACKGROUND: Moist wound treatment improves healing at a possibly increased risk of bacterial infection and many local antiseptics impair healing. A moist treatment modality with efficient antimicrobial activity would be desirable. METHODS: In this monocentric, randomized, observer blinded, phase III study, a new hydrosome polyvinyl-pyrrolidone (PVP)-iodine preparation in hydrogel containing iodine in a 3% concentration (Repithel) was investigated for its effect on epithelialization in patients receiving meshed skin grafts. Grafts of 167 patients (donor site defects, burn wounds, or chronic defects) were dressed either with Repithel (n=83) covered with a gauze (Jelonet), or Jelonet-gauze only (n=84) until healing. RESULTS: Grafts receiving Repithel healed significantly earlier (9.4 days versus 12.4 days; p<0.0001) and faster than controls as measured by neo-epithelialization of mesh holes between days 7 and 11 (91.2+/-22.8% versus 82.3%+/-28.6, p<0.0001). A subgroup analysis showed that the effects on grafted burn wounds (p=0.0042) and chronic defects (p<0.0001) was more significant than on donor sites. Also a higher take rate of grafts (p=0.0053) and a reduced loss of grafts was observed with Repithel treatment (8 grafts versus 20 grafts) (p=0.0063, respectively). Smokers had improved graft take (p=0.0069) and higher rate of epithelialization (p=0.0040) compared to smokers of the control group. CONCLUSIONS: The results demonstrate significant clinical advantages of Repithel. This new local wound healing drug combines antisepsis and wound moisture efficiently resulting in significantly enhanced epithelialization, decreased transplant losses, and significantly improved healing especially in smokers.

Anti-Infective Agents, Local↗

PubMed2006

[Efficacy of treatment with Repithel and Jelonet in comparison to treatment with Jelonet alone - a randomized clinical trial in patients receiving meshed skin grafts].

UNLABELLED: Moist wound treatment is a well recognized method for the treatment of aseptic acute and chronic wounds. While the moist environment is beneficial to the woundhealing process, it also increases the risk of bacterial superinfection. We here report on the results of a clinical phase-III-study in which we tested the effect of a new PVP-iodine liposomal hydrogel (Repithel) on split-thickness skin grafts. This formulation optimizes moist wound treatment by improving the cell proliferation rate while preventing wound infection. AIM: The aim of this phase-III-study was to analyse the efficacy and tolerance of Repithel in patients receiving meshed skin grafts. METHODS: 167 patients with transplantation wounds were either treated with lipid gauze alone (control group) or with lipid gauze and Repithel. In both groups the extent of neoepithelization, the frequency and severity of graft losses and the time until complete wound closure was achieved were determined. Analysis of the re-epithelization was achieved by photoplanimetry. Impedance measurements gave additional information on the regeneration of the epidermal barrier. RESULTS: Wounds receiving Repithel showed a significantly faster neoepithelisation than wounds which were treated with lipid gauze alone. Treatment with Repithel significantly reduced both the number of graft losses and the size of area lost. The time until wounds were closed completely was significantly shorter in patients receiving Repithel than in controls. The positive effects of Repithel on wound healing were especially observed in smokers, patients with chronic wounds, burns or infected wounds. CONCLUSIONS: Repithel supports healing of meshgraft transplants and reduces the risk of graft loss. Patients who heal poorly benefit particularly from the Repithel treatment.

Anti-Infective Agents, Local↗

PubMed2006

Repithel: removing the barriers to wound healing.

BACKGROUND: Various standardized and/or validated models exist to test wound healing products. This article discusses their usefulness in clinical practice. OBJECTIVES: Major barriers to wound healing have been identified after intense interaction of research and practitioners. Although extensively tested, wound healing products are still associated with trial and error due to the high variability and complexity associated with the treatment of wounds. Therefore, the results of preclinical testing are compared and contrasted with clinical observations of a liposomal hydrogel containing 3% povidone-iodine (Repithel, PVP-ILH) to assess their expressiveness and to give the practitioner more guidance in application. METHODS: Testing of PVP-ILH included physicochemical testing according to ISO norms, testing in in vitro and in vivo models. The obtained results are compared to the clinical profile of the obtained product in randomized controlled trials and ultimately expressive case studies. RESULTS: PVP-ILH displays good local tolerance, the basis for use in sensitive and predamaged tissue. As observed in laboratory testing, it readily provides moisture and takes up limited amounts of moisture. This was also seen in the clinical testing, as the ability to keep wounds moist and incorporate a certain -- but not large -- amount of exudates. Clinical results also show clean, well-debrided wounds, an effect that (in the absence of an established model for wound cleansing) was traced to the hydrogel component carbomer. DISCUSSION: Recent consensus advocates the concept of wound bed preparation as a systematic approach to removing barriers to healing (TIME). Based on the results, tissue (removing non-viable tissue and debris) and moisture (balance) can now be better understood, and infection/inflammation (control) and edge (progressing, non-advancing or undermining wound edges) are reviewed together with previously published data to assess all aspects potentially impeding wound healing. CONCLUSION: PVP-ILH successfully removes barriers to wound healing, thus laying the foundation to high-quality wound closure. Results from many scientific disciplines can help the user to better understand a product, standardization of testing is the only way of making results comparable.

Absorption↗

PubMed2005

Influence of D-arabitol and ribitol on neuronal network activity.

To date, two new defects in the pentose phosphate pathway have been identified in patients with abnormalities in their polyol profiles. Some of them presented with neurological symptoms of so far unknown aetiology. The pathophysiological role of polyols, e.g. in the brain, is relatively unknown. We tested the neurotoxicity of polyols using a 'neurochip' model. After exposure of cortical rat neurons to D-arabitol and ribitol in increasing concentrations up to 10 mmol/L, the electrophysiological activity was measured. No acute effect on the spontaneous network activity of cortical neurons was observed. We speculate that polyols have only secondary effects on brain dysfunction.

Animals↗

PubMed2002

Lung deposition of salbutamol in healthy human subjects from the MAGhaler dry powder inhaler.

The MAGhaler (Mundipharma GmbH) is a multidose dry powder inhaler (DPI) containing a novel formulation of drug and lactose compacted by an isostatic pressing technique (GGU GmbH). On actuation, a precise dose is metered from a compacted ring-shaped drug tablet. In this study, the lung deposition of salbutamol from this device has been assessed. Ten healthy non-smoking subjects completed a two-way cross-over study assessing the pulmonary deposition of salbutamol (200 microg) from the MAGhaler at high (60 l/min) and low (30 l/min) peak inhaled flow rates (PIFRs), representing maximal and sub-maximal inspiratory efforts. The formulation was radiolabelled with 99mTc, and lung and oropharyngeal depositions were quantified by gamma scintigraphyThe mean (SD)% ofthe delivered dose deposited in the lungs was 26.4 (4.3)% at 60 l/min and 21.1 (5.1)% at 30 l/min (P < 0.05), corresponding to mean lung depositions of 52.8 and 42.2 microg salbutamol, respectively. The distribution of drug within different lung regions did not vary significantly with inhaled flow rate. The data provided proof of concept for the novel inhaler device and the innovative drug formulation. In comparison with previous deposition data obtained with other DPIs, the lung deposition was relatively high, relatively reproducible (coefficient of variation 16% at 60 l/min) and relatively insensitive to the change in peak inhaled flow rate.

Adult↗

PubMed2002

Antimicrobial effectiveness of povidone-iodine and consequences for new application areas.

The microbicidal action spectrum of povidone-iodine (PVP-I) is broad - even after short onset times. Unlike local antibiotics and other antiseptic substances, no resistance develops. The high degree of bactericidal efficiency in respect of highly resistant gram-positive pathogenic micro-organisms, such as methicillin-resistant Staphylococcus aureus (MRSA) and enterococcus strains, is particularly significant for hospital hygiene. An in vitro study with 10 genotypically different MRSA isolates showed an optimum bactericidal effect (logarithmic reduction factor value >5) without protein load after just 30 s exposure and even in a dilution of Betaisodona solution (Mundipharma GmbH) of 1%. With protein load (0.2% albumin), the optimum in microbicidal effectiveness shifts to concentrations > or = 10% Betaisodona solution referring to an exposure time of 30 s. Since recent results are now also available on the toxicological safety of PVP-I preparations for the ciliated epithelium of the nasal mucosa and the good tolerability on skin and other mucous membranes is a known factor, a controlled clinical study is currently being carried out to eliminate colonizations of MRSA. Evidence has also recently been produced of the antiviral activity of PVP-I against herpes simplex, adeno- and enteroviruses, as well as its high degree of efficiency against Chlamydia. Hence alongside the classical fields of application, such as the disinfection of the skin and hands, mucosa antisepsis and wound treatment, there are also useful indications for the substance, i.e. rinsing of body cavities and joints and application to the eye.

Adenoviridae Infections↗

PubMed2000

An innovative topical drug formulation for wound healing and infection treatment: in vitro and in vivo investigations of a povidone-iodine liposome hydrogel.

BACKGROUND: In topical wound treatment, the combination of anti-infectious therapy and a healing-promoting moisturization has not been accomplished yet. OBJECTIVE: Evaluation of a new topical drug consisting of a povidone-iodine (PVP-I) liposome hydrogel allowing for both antiseptic and moist treatment. METHODS: Pharmaceutical formulation of a complex of PVP-I (3%) and phosphatidylcholine in a hydrogel. In vitro, interaction of the complex with relevant micro-organisms was analysed by electron microscopy. Antimicrobial activity was investigated using Staphylococcus aureus in a suspension test. Tissue toxicity was examined by an explantation test in a rodent model. A randomized clinical study on efficacy and tolerability in wound healing was carried out on 35 patients with mesh grafts in parallel groups (PVP-I liposome hydrogel vs. Bactigras) for proof of concept in humans. RESULTS: A direct interaction of the PVP-I liposomes with micro-organisms by attachment to the cell surface was documented. A significantly better microbicidal activity and tissue tolerability of the PVP-I liposome hydrogel compared to conventional PVP-I formulations was shown. The results of the clinical study, especially measurements of neo-epithelization per time and transplant loss, demonstrate significant differences in favour of the PVP-I liposome hydrogel. CONCLUSION: The novel PVP-I liposome hydrogel combines microbicidal and wound healing activities resulting in enhanced epithelization.

Anti-Infective Agents, Local↗

PubMed1998

[Prevention of radiochemotherapy-induced mucositis. Value of the prophylactic mouth rinsing with PVP-iodine solution].

BACKGROUND: Oral mucositis is a frequent complication of radiochemotherapy. The origin of radiation-induced mucosa lesions is of iatrogenic nature although further development of mucositis is essentially influenced by infection. It can be assumed that disinfection measures should decrease the severity of mucositis induced by radiochemotherapy. Therefore, in a prospective randomised study the efficacy of prophylactic oral rinsing with a disinfection agent was investigated. PATIENTS AND METHOD: An open, randomised, prospective comparative trial was conducted with 40 patients undergoing radiochemotherapy of head and neck region due to malignant disease. The treatment scheme consisted of irradiation to tumor region and adjacent lymph nodes with a total dose of 71.3 Gy and simultaneous chemotherapy with carboplatin (60 mg/m2) on days 1 to 5 and 29 to 34. In all patients, a prophylaxis of mucositis with nystatine, rutosides, panthenol and immunoglobulin was undertaken. In addition, 20 patients rinsed oral cavity 4 times daily with povidone-iodine-solution, the comparative group rinsed with sterile water. Clinical examination of the oral mucosa was performed weekly. Onset, grading and duration of mucositis were used as main variables. RESULTS: Clinically manifested oral mucositis was observed in 14 patients of the iodine group (mean grading: 1.0) and all 20 patients of the control group (mean grading: 3.0). Total duration (mean) of clinically observed mucositis was 2.75 weeks in treatment patients and 9.25 in control patients. Median AUC (area under curve for grade vs duration) was 2.5 in iodine rinsing patients and 15.75 in control patients. All differences found between the 2 groups were statistically significant. Increased iodine incorporation was not observed. A pathological increase of thyroid hormone levels in the iodine group was not found. CONCLUSIONS: The gained results indicate that incidence, severity and duration of radiochemotherapy-induced mucositis can be significantly reduced by oral rinsing with povidone-iodine performed additionally to the standard prophylaxis scheme.

Adult↗

PubMed1998

Prophylaxis with povidone-iodine against induction of oral mucositis by radiochemotherapy.

Oral mucositis is a frequent complication of radiochemotherapy. The origin of radiation-induced mucosal lesions is iatrogenic in nature, although further development of mucositis is essentially influenced by infection. It can be assumed that disinfection measures should decrease the severity of mucositis induced by radiochemotherapy. Therefore, in a prospective randomised study the efficacy of prophylactic oral rinsing with a disinfection agent was investigated. A randomised, prospective comparative trial was conducted with 40 patients undergoing radiochemotherapy of the head and neck region because of malignant disease. The treatment scheme consisted of irradiation to the tumour region and adjacent lymph nodes, with a total dose of 71.3 Gy, and simultaneous chemotherapy with carboplatin (60 mg/m2) on days 1-5 and 29-34. In all patients mucositis prophylaxis with nystatin, rutosides, panthenol and immunoglobulin was undertaken. In addition, 20 patients rinsed the oral cavity 4 times daily with povidone-iodine solution, while the group for comparison rinsed with sterile water. Clinical examination of the oral mucosa was performed weekly. Onset, grading and duration of mucositis were used as the main variables. Clinically manifest oral mucositis was observed in 14 patients in the iodine group (mean grading: 1.0) and in all 20 patients in the control group (mean grading: 3.0). The total duration (mean) of clinically observed mucositis was 2.75 weeks in treatment patients and 9.25 weeks in control patients. Median AUC (area under curve for grade vs duration) was 2.5 in the iodine rinsing patients and 15.75 in control patients. All differences found between the two groups were statistically significant. Increased iodine incorporation was not observed. A pathologic rise in thyroid hormone levels was not found in the iodine group. The results obtained indicate that incidence, severity and duration of radiochemotherapy-induced mucositis can be significantly reduced by oral rinsing with povidone-iodine in addition to the standard prophylaxis scheme. It can be concluded that rinsing with povidone-iodine is an easy, cheap and safe prophylactic method and can be recommended as a supportive treatment during antineoplastic treatment of the head and neck region.

Adult↗

PubMed1998

[Molecular effects of a microbicidal substance on relevant microorganisms: electron microscopic and biochemical studies on povidone-iodine].

The microbicidal activity of the broad spectrum antimicrobial agent povidone-iodine is due to the strong oxidizing effects of free iodine on functional groups of amino acids, nucleotides and double bonds of unsaturated fatty acids. While the chemical mechanism of action of PVP-iodine is well understood, the actual sequence of events on the cellular and molecular level that causes rapid cell death has not been fully understood. The aim of this study was to elucidate effects of povidone-iodine on cell ultrastructure by electron microscopy and to monitor changes in enzyme activity and nucleotide efflux. Staphylococcus aureus, E. coli and C. albicans, medically relevant gram-positive, gram-negative and yeast micro-organisms, served as models. In the presence of povidone-iodine, rapid partitioning of the cytoplasm and pronounced coagulation of nuclear material was noted. Especially C. albicans exhibited a rapid, dose-dependent "loosening" of the cell wall; cells remained intact without lysis, rupture or wall breakage. Changes in beta-galactosidase and nucleotide concentrations were measured in E. coli. A rapid and dose-dependent loss of cellular beta-galactosidase activity was found, with no increase in the supernatant; loss of cellular nucleotides corresponded with an increase in the supernatant. Electron microscopy and biochemical observations support the conclusion that povidone-iodine interacts with cell walls of micro-organisms causing pore formation or generating solid-liquid interfaces at the lipid membrane level which lead to loss of cytosol material, in addition to enzyme denaturation. The chemical mechanism of action explains the fact that povidone-iodine does never generate resistance in micro-organisms.

Anti-Infective Agents, Local↗

PubMed1998

[Antibacterial effectiveness of povidone-iodine (Betaisodona) against highly resistance gram positive organisms].

Antiseptics that are locally applicable gain in significance due to their reliable microbicidal effectiveness and especially due to the rising incidence of highly resistant bacteria. This is because systemically applied antibiotics are not sufficient in eradicating superficial mucodermal bacteria and locally applied antibiotics can cause new resistance rapidly. The aim of this study was to demonstrate the microbicidal effectiveness of Poly(1-vinyl-2-pyrrodlidon)-iodine (PVP-iodine) against ten genotypical different methicillin resistant Staphylococcus aureus-(MRSA-) and five Enterococcus faecium-strains in a quantitative suspension test. The effectiveness of PVP-iodine with protein load (0.2% and 2% albumin) was tested against three MRSA strains. Without any protein load best microbicidial activity (KRt-value > 5) was obtained with concentrations in the range between 1-10% of the original Betaisodona solution after 30s exposure time. With protein load (0.2% albumin) the optimum in microbicidal effectiveness shifts to concentrations > or = 10% Betaisodona solution referring to an exposure time of 30s. With a protein load up to 2% albumin and an exposure time of 30s the bactericidal activity of the undiluted Betaisodona solution is already satisfying, while the 10% solution is not active till an exposure time of 5 min. Summing up PVP-iodine is recommended as a local mucodermal antiseptic against highly resistant gram positives.

Anti-Infective Agents, Local↗

PubMed1997

Povidone-iodine in antisepsis--state of the art.

The natural element iodine has been used for more than 150 years to prevent infection and treat wounds. Yet only due to the development of iodophors has it become possible to use this highly efficient microbicide in a wide range of medical applications. The antimicrobial spectrum is universal. Its efficiency against clinically and epidemiologically significant new pathogens, such as methicillin-resistant Staphylococcus aureus and Enterococcus sp. has also been validated. No development of resistance has been determined. New data are also available on the excellent local tolerability of Betaisodona (povidone-iodine) preparations. On these grounds, a number of clinical fields exist in prophylaxis and therapy, for either once only or repeated applications: the disinfection of hands and skin, mucosa antisepsis, intra- and postoperative wound treatment, therapy of skin infections, burns and chronic wounds.

Anti-Infective Agents, Local↗

PubMed1997

Effects of Betaisodona on parameters of host defense.

The numbers of patients in intensive care units, with immunosuppression, and of elderly people increase in parallel with antibiotic-resistant microorganisms. Therefore the demand for an effective antisepsis increases. Moreover, it became evident that the pathophysiology and the outcome of infection are dependent on the properties of the microorganisms, e.g. synthesis of endo- and exotoxins, and on the host defense, the immune system. In addition to the microbicidal action, we studied the effects of povidone-iodine (PVP-I, Betaisodona) on the generation, release and activity of exotoxins (alpha-hemolysin, phospholipase C, lipase), as well as on granulocyte-derived tissue-destructive enzymes (elastase, beta-glucuronidase) and microbial-induced cytokine generation from human neutrophils. Our results clearly show that PVP-I does not only kill a wide range of bacteria but also inhibits the generation and release of bacterial exotoxins; furthermore, it also inactivates bacterial exotoxins as well as granulocyte-derived tissue-destructive enzymes and cytokines. These data support the usefulness and efficacy of PVP-I as an effective therapeutic agent to combat infection.

Aged↗

PubMed1997

Povidone-iodine to prevent mucositis in patients during antineoplastic radiochemotherapy.

In an open study, the efficacy of povidone-iodine in the prophylaxis of mucositis during antineoplastic radiochemotherapy was determined. 40 patients were randomly assigned to a treatment or control group (each 20 patients). All patients received standard prophylaxis of mucositis with nystatin, dexpanthenol, rutoside and immunoglobulin. In addition, the patients of the treatment group performed 4 times daily rinsing with povidone-iodine, the control patients with sterile water. Clinical examination of the oral mucosa was performed weekly during the radiation period and up to 6 weeks after the end of therapy. Oral mucositis was observed in 14 patients of the treatment group (mean grading: 1.0) and in all 20 patients of the control group (mean grading: 3.0). The mean onset of mucositis was after 2.25 weeks in treatment patients and 1.5 weeks in control patients. The mean total duration of mucositis was 2.75 weeks in treatment patients and 9.25 weeks in control patients. The mean AUC values were 2.5 in treatment patients and 15.75 in control patients. All findings were statistically significantly different between the two groups. It is concluded that rinsing with povidone-iodine reduces the incidence, severity and duration of oral mucositis during antineoplastic radiochemotherapy.

Adult↗

PubMed1997

Povidone-iodine liposomes--an overview.

In recent years, liposomes have been increasingly explored as novel drug delivery systems, and several liposome-based drug products have been approved in Europe, the USA and Japan. Depending on size, composition and surface characteristics, liposomes interact specifically with biological structures. Liposomal drug products provide a topical activity at the desired locus of action and are deemed more effective and less toxic than conventional drug formulations. The combination of povidone-iodine (PVP-I) and liposomes unites the exceptional microbicidal activity of the antiseptic substance with the excellent tolerability and lack of immunogenicity of liposomes; in addition, liposomes provide a moist molecular film for the wound environment. The multilamellar vesicles act as microreservoirs hence prolonging the release of the active ingredient. Although no commercial product for repeated application on the eye is currently available, PVP-I has been used in ophthalmology not only for pre- and postoperative antisepsis, but also for the treatment of bacterial and viral conjunctivitis and for prophylaxis against ophthalmia neonatorum. For these indications, liposomal formulations with 2.5 and 5.0% PVP-I were developed. These eye drops are isotonic with tear fluid at pH 6. First in vitro tests demonstrated an excellent antimicrobial efficacy, and a placebo-controlled clinical study on volunteers showed a very good local tolerability. A study on rabbits demonstrated positive results of the PVP-I liposome eye drops compared to placebo and the broadspectrum antibiotic Polyspectran in a standardized model of Staphylococcus aureus deep eye infection. The other aim is a well-tolerated liposomal PVP-I hydrogel for improved antiseptic wound treatment with moisturizer. It has been reported that liposomes are enriched at the wound bottom for direct action against infection and support of wound healing. An animal study on the efficacy and tolerability of different formulations of a hydrogel with PVP-I liposomes in deep dermal burn wounds has indicated an outstanding quality of wound healing with smooth granulation tissue, less inflammation, less wound contraction and no hyperkeratotic reactivity, especially with the 3% PVP-I liposome formulation.

Administration, Cutaneous↗

PubMed1997

Molecular effects of povidone-iodine on relevant microorganisms: an electron-microscopic and biochemical study.

The aim of this study was to elucidate the effects of povidone-iodine (PVP-I) on cell ultrastructure by electron microscopy and to monitor changes in enzyme activity and nucleotide efflux. Staphylococcus aureus, Escherichia coli and Candida albicans, medically relevant gram-positive, gram-negative and yeast microorganisms, served as models. In the presence of PVP-I, rapid partitioning of the cytoplasm and pronounced coagulation of nuclear material was noted. E. coli and S. aureus showed no major structural wall damage. C. albicans exhibited a rapid, dose-dependent 'loosening' of the cell wall; cells remained intact without lysis, rupture or wall breakage. Changes in beta-galactosidase and nucleotide concentrations were measured in E. coli. A rapid and dose-dependent loss of cellular beta-galactosidase activity was found, with no increase in the supernatant; loss of cellular nucleotides corresponded with an increase in the supernatant. Electron-microscopic and biochemical observations support the conclusion that PVP-I interacts with cell walls of microorganisms causing pore formation or generating solid-liquid interfaces at the lipid membrane level which lead to loss of cytosol material, in addition to enzyme denaturation.

Anti-Infective Agents, Local↗

PubMed1997

Analgesia by dihydrocodeine is not due to formation of dihydromorphine: evidence from nociceptive activity in rat thalamus.

Dihydrocodeine is increasingly used in slow-release preparations for the treatment of chronic pain on step 2 of the "analgesic ladder" of the World Health Organization. Dihydrocodeine is suggested to act after O-demethylation to dihydromorphine. To test this possibility, experiments were carried out on rats under urethane anesthesia in which nociceptive activity was evoked by electrical stimulation of afferent C fibers in the sural nerve and recorded from neurons in the ventrobasal complex of the thalamus. Dihydrocodeine administered by intravenous injection reduced the evoked nociceptive activity in a dose-dependent manner. Like morphine, dihydrocodeine was capable of completely suppressing the evoked activity. Maximum depression was caused by 2 mg/kg, and the ED50 is 0.47 mg/kg. Naloxone (0.2 mg/kg) reversed the effect of dihydrocodeine (2 mg/kg). To inhibit O-demethylation of dihydrocodeine to dihydromorphine, metyrapone or cimetidine (50 mg/kg) was injected intraperitoneally 20 min before dihydrocodeine (1 and 2 mg/kg). This failed to markedly reduce the effect of dihydrocodeine. Dihydromorphine injected intravenously also reduced the evoked activity in a dose-dependent way. Maximum depression occurred at a dose of 4 mg/kg, and the ED50 is 0.97 mg/kg. Dihydrocodeine and dihydromorphine were equieffective when administered by intrathecal injection at a dose of 100 microg. It is concluded that dihydrocodeine causes analgesia independent of biotransformation to dihydromorphine.

Analgesics, Opioid↗

PubMed1996

Depression by morphine-6-glucuronide of nociceptive activity in rat thalamus neurons: comparison with morphine.

To assess the contribution of the active metabolite of morphine, morphine-6-glucuronide (M6G), to the analgesic effect of systemically administered morphine, experiments were carried out on rats under urethane anesthesia in which nociceptive activity was evoked by electrical stimulation of afferent C fibers in the sural nerve and recorded from single neurons in the ventrobasal complex of the thalamus. Intravenous (i.v.) injections of morphine completely blocked the activity at doses of 500 and 1000 micrograms/kg, the ED50 being 44 micrograms/kg. M6G administered by i.v. injection reduced the evoked nociceptive activity only by about 40% at 80 and 160 micrograms/kg, the ED50 being 6 micrograms/kg. After intrathecal (i.t.) injection, morphine produced maximum depression of 55% of the control activity at 20 micrograms; the ED50 is 18 micrograms. M6G injected i.t. produced maximum depression of 40% at doses ranging from 0.2 to 10 micrograms. The ED50 of M6G i.t. is below 0.2 micrograms. The effects of morphine and M6G were reversed by naloxone (200 micrograms/kg i.v.). The results show that M6G is more potent than morphine, regardless of the route of administration, while morphine is more effective when injected i.v. Due to the low efficacy of M6G, it seems unlikely that this glucuronide contributes substantially to the analgesic effect of morphine when renal function is normal. The results also make evident that the maximum effect of morphine results from an action at spinal and supraspinal sites.

Animals↗