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Systemic Absorption (systemic + absorption)
Selected AbstractsLow Systemic Absorption and Good Tolerability of Pimecrolimus, Administered as 1% Cream (Elidel®) in Infants with Atopic Dermatitis , A Multicenter, 3-Week, Open-Label StudyPEDIATRIC DERMATOLOGY, Issue 5 2005Doris Staab M.D. Here we evaluate pimecrolimus blood concentrations and tolerability to pimecrolimus cream 1% in 22 infants below 2 years of age with atopic dermatitis (10,92% body surface area affected at baseline). Efficacy was assessed as a secondary objective. Pimecrolimus cream 1% was applied twice daily for 3 weeks. Blood concentrations were low, typically (96% of total 100 concentrations measured) below 2 ng/mL, the majority (71%) remaining below 0.5 ng/mL. The highest concentration observed was 2.26 ng/mL. At steady state, there was no indication of accumulation. Pimecrolimus was well tolerated locally and systemically, with no serious adverse events recorded. Most adverse events recorded (35 in 17/22 patients) were typical of the young pediatric population studied, of mild to moderate severity, and not considered to be study-medication related, with the exception of four local adverse effects limited to the site of cream application. No clinically relevant change was observed in physical examination, vital signs, or laboratory safety parameters. A rapid onset of therapeutic effect was observed within the first four days of treatment. Pimecrolimus cream 1% is well tolerated in infants 3 to 23 months of age treated for 3 weeks, and results in minimal systemic exposure. [source] Synthetic Tannins in Dermatology,A Therapeutic Option in a Variety of Pediatric DermatosesPEDIATRIC DERMATOLOGY, Issue 3 2007Regina Fölster-Holst M.D. The therapeutic effects of synthetic tannins are based on their tanning action as well as on their antimicrobial, anti-inflammatory, and antipruritic effects. In terms of pharmacology and clinical applicability, synthetic tannins are particularly versatile substances. They have also been used as steroid-free, anti-inflammatory treatment alternatives, especially in pediatric dermatoses. Systemic absorption is not to be expected. Because of their high safety profile and good tolerance, they are appropriate for the treatment of all age groups. Thus, synthetic tannins can be safely used for infants and children and also during pregnancy and lactation. [source] Safety of Lidocaine 15% and Prilocaine 5% Topical Ointment Used as Local Anesthesia for Intense Pulsed Light TreatmentDERMATOLOGIC SURGERY, Issue 7 2010J. ALASTAIR CARRUTHERS MD BACKGROUND Literature cautions against applying lidocaine 15%/prilocaine 5% over an area larger than 300 cm2. The area of the face, neck, and chest is 400 cm2 or greater. OBJECTIVE To investigate the safety of lidocaine 15%/prilocaine 5% topical anesthetic ointment used as anesthesia for intense pulsed light (IPL) treatment. METHODS AND MATERIALS Lidocaine 15%/prilocaine 5% ointment was applied to the face only (n=10) for 30 ± 15 minutes or to the face, neck, and chest (n=10) for a total of 60 ± 15 minutes before IPL. Blood lidocaine and prilocaine levels were measured. Adverse events were recorded. RESULTS For the entire cohort, blood was drawn 25.6 ± 6.6 minutes after IPL was completed. In the face only group, the mean lidocaine level was 0.122 ± 0.125 ,g/mL, and the mean prilocaine level was 0.048 ± 0.029 ,g/mL. In the face, neck, and chest group, the mean lidocaine level was 0.272 ± 0.208 ,g/mL, and the mean prilocaine level was 0.087 ± 0.060 ,g/mL. No adverse events related to systemic toxicity were observed or reported to the nurse. At the 24-hour follow-up, no subject reported symptoms of systemic toxicity after leaving the clinic. CONCLUSION Under the conditions of this study, topical lidocaine 15%/prilocaine 5% produces low levels of systemic absorption. The authors have indicated no significant interest with commercial supporters. [source] Oral budesonide for the therapy of post-liver transplant de novo inflammatory bowel disease: A case series and systematic review of the literatureINFLAMMATORY BOWEL DISEASES, Issue 12 2008A. Sidney Barritt IV MD Abstract Background: The therapy for posttransplant IBD is clinically challenging. Patients receiving liver transplants are immunosuppressed to prevent rejection, but via an unknown mechanism develop de novo IBD in spite of receiving some of the same medications used for therapy in traditional IBD. In the published literature most of the patients who developed de novo IBD were treated with traditional corticosteroids. Exposure to systemic corticosteroids increases risks of infection, diabetes mellitus, and osteoporosis among other complications. Budesonide, a luminally active steroid with low systemic absorption, is an established therapeutic agent for IBD that should receive special considerations as first-line therapy in this patient population. Methods: We describe 3 cases of de novo IBD after liver transplantation. None of these patients had a history of IBD prior to their transplant. All 3 were treated with oral budesonide in lieu of systemic corticosteroids. Additionally, a Medline MeSH search was performed using the terms "inflammatory bowel disease" and "liver transplant" as part of a systematic review of the literature. Results: All 3 cases of de novo post transplant IBD went into clinical remission with oral budesonide. The Medline search ultimately revealed 19 case reports, case series or retrospective reviews on de novo post liver transplant IBD. Most reports focused on the diagnosis and risk factors and did not have an emphasis on therapy. Conclusions: Given the track record for budesonide in traditional IBD, and its documented efficacy and systemic steroid-sparing benefit, in our opinion this drug should be considered first-line therapy for de novo posttransplant IBD. (Inflamm Bowel Dis 2008) [source] Effect of dimethyl-,-cyclodextrin concentrations on the pulmonary delivery of recombinant human growth hormone dry powder in ratsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2008Monireh Jalalipour Abstract The aim of this article is to prepare and characterize inhalable dry powders of recombinant human growth hormone (rhGH), and assess their efficacy for systemic delivery of the protein in rats. The powders were prepared by spray drying using dimethyl-,-cyclodextrin (DM,CD) at different molar ratios in the initial feeds. Size exclusive chromatography was performed in order to determine protecting effect of DM,CD on the rhGH aggregation during spray drying. By increasing the concentration of DM,CD, rhGH aggregation was decreased from 9.67 (in the absence of DM,CD) to 0.84% (using DM,CD at 1000 molar ratio in the spray solution). The aerosol performance of the spray dried (SD) powders was evaluated using Andersen cascade impactor. Fine particle fraction values of 53.49%, 33.40%, and 23.23% were obtained using DM,CD at 10, 100, and 1000 molar ratio, respectively. In vivo studies showed the absolute bioavailability of 25.38%, 76.52%, and 63.97% after intratracheal insufflation of the powders produced after spray drying of the solutions containing DM,CD at 10, 100, and 1000 molar ratio, respectively in rat. In conclusion, appropriate cyclodextrin concentration was achieved considering the protein aggregation and aerosol performance of the SD powders and the systemic absorption following administration through the rat lung. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5176,5185, 2008 [source] Nasal administration of low molecular weight heparinJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2002John Arnold Abstract The main objective of this study was to determine if the systemic absorption of therapeutic amounts of heparin was possible following nasal administration. Sprague-Dawley rats received nosedrops containing a low molecular weight heparin (LMWH) or unfractionated heparin (UFH) formulated with or without tetradecylmaltoside (TDM). TDM is a nonionic surfactant that has been previously shown to be a potent absorption enhancer in studies with peptide drugs. LMWH/UFH absorption was determined by measuring plasma anti-Factor Xa activity. The inclusion of 0.25% TDM in nasal formulations containing LMWH resulted in a significant increase in the Cmax and area under the curve (AUC) of anti-Factor Xa activity when compared to LMWH formulated in saline alone. The addition of TDM to a nasal formulation containing UFH resulted in a much smaller increase in the Cmax and the AUC of anti-Factor Xa activity. The absolute bioavailability of LMWH was increased from 4.0,±,0.4% in the absence of TDM to 19,±,0.3% in the presence of TDM. The reversibility of the absorption enhancing effect of TDM was studied by applying LMWH nasally 60 or 120 min after the enhancer. The effect of TDM on the nasal epithelia appeared to be rapidly reversible. In conclusion, nasal delivery of LMWH, but not UFH, was successful when an absorption enhancer was included to increase nasal permeability. © 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1707,1714, 2002 [source] Tacrolimus is a class II low-solubility high-permeability drug: The effect of P-glycoprotein efflux on regional permeability of tacrolimus in ratsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2002Shigeki Tamura Abstract The objective of this study is to investigate the role of P-glycoprotein (P-gp), a membrane efflux pump associated with multidrug resistance (MDR) and a known substrate for tacrolimus, in determining the regional intestinal permeability of tacrolimus in rats. Thus, isolated segments of rat jejunum, ileum, or colon were perfused with tacrolimus solutions containing polyethoxylated hydrogenated castor oil 60 surfactant, and with or without verapamil, a P-gp substrate used to reverse the MDR phenotype. The results indicated that the intrinsic permeability of tacrolimus in the jejunum, calculated on the basis of the concentration of non-micellized free tacrolimus, was quite high (,,1.4,×,10,4 cm/s). The apparent permeability (Papp) in the jejunum was unaffected by the presence of verapamil; however, the Papp in the ileum and the colon increased significantly in the presence of verapamil and were similar to the values observed in the jejunum. The results suggest that systemic absorption of tacrolimus from the gastrointestinal tract could be significantly affected by P-gp efflux mechanisms. It is also possible that differences in P-gp function at various intestinal sites in a subject or at a given intestinal site in various subjects could lead to large intra- and interindividual variability in bioavailability of tacrolimus following oral administration. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:719,729, 2002 [source] Oral, colonic-release low-molecular-weight heparin: an initial open study of Parnaparin-MMX for the treatment of mild-to-moderate left-sided ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008L. PASTORELLI Summary Background, Efficacy of heparin and low-molecular-weight heparins (LMWHs) in inflammatory bowel disease (IBD) treatment has been suggested. The multimatrix oral formulation MMX releases active drugs in the colon, avoiding systemic absorption. Parnaparin sodium is the LMWH chosen to be carried in the MMX formulation. Aim, To assess the safety of three different oral dosages (70, 140 and 210 mg once daily) of Parnaparin-MMX (CB-01-05) in left-sided ulcerative colitis (UC). Methods, Left-sided UC patients, with a mild-to-moderate relapse were enrolled. All patients received Parnaparin-MMX for 8 weeks. Clinical Activity Index (CAI), Disease Activity Index (DAI), Endoscopic Activity Index and IBD-QoL were assessed throughout the study. A strict clinical and laboratory follow-up, including assessment of anti-factor Xa activity, was performed. Clinical remission was defined as CAI <4. Results, Ten UC patients were enrolled. One patient retired for clinical deterioration. No relevant side effects, including either interference with haemostasis parameters or increased bleeding, were observed. At the end of the treatment, seven patients (70%) were in clinical remission, only one achieving endoscopic healing. Mean final CAI, DAI and IBD-QoL scores were significantly improved from baseline. Conclusions, Parnaparin-MMX appears to be a safe treatment option in mild-to-moderate UC. Controlled studies are warranted. [source] The Safety and Efficacy of Tacrolimus Ointment in Pediatric Patients with Atopic DermatitisPEDIATRIC DERMATOLOGY, Issue 5 2010Alexandra D. McCollum M.D. It is a chronic disorder, characterized by intermittent flares and phases of remission. Treatment regimens often require multiple therapies. These can vary between patients, and in an individual patient, depending on the state of disease. The traditional treatment for AD flares is topical corticosteroids, which are fast acting and effective for relief of symptoms, but may cause adverse effects, including those resulting from systemic absorption, particularly in children. Topical calcineurin inhibitors (TCIs) are alternative treatments for AD. Tacrolimus ointment, a TCI, is approved for patients aged 2 years and older. Multiple studies have shown that tacrolimus is effective for short-term relief of symptoms in pediatric patients with AD. Long-term trials have demonstrated that the effectiveness of tacrolimus is maintained for up to 4 years in children. Additional studies have revealed that long-term intermittent use of tacrolimus as part of maintenance therapy can prevent AD flares. Tacrolimus has a low potential for systemic accumulation, and analysis of long-term studies indicates that it has a good safety profile. Treatment with tacrolimus, alone or in combination with topical corticosteroids for acute flares, may be a useful option for long-term management of AD in pediatric patients. [source] Blood concentrations, tolerability and efficacy of pimecrolimus cream 1% in Japanese infants and children with atopic dermatitisTHE JOURNAL OF DERMATOLOGY, Issue 4 2007Lawrence F. EICHENFIELD ABSTRACT Pimecrolimus cream 1% is a topical calcineurin inhibitor for the treatment of atopic dermatitis. Minimal systemic exposure to pimecrolimus has been previously observed in Caucasian pediatric patients treated with the cream twice daily for up to 1 year. The objective of this open-label, non-comparative, multicenter study was to assess the systemic exposure, tolerability and efficacy of pimecrolimus cream 1% when used twice daily for 3 weeks in pediatric patients of Japanese background. The patient cohort consisted of 17 Japanese infants and children (age range, 3.6 months to 11.6 years) with atopic dermatitis of at least mild severity affecting ,10% of the total body surface area (range, 10,48%). Pimecrolimus cream 1% was applied twice daily for 3 weeks. Blood levels of pimecrolimus were determined on days 1, 10 and 22. Safety and tolerability were evaluated by monitoring adverse events, laboratory parameters, physical condition and vital signs. Efficacy parameters included the Eczema Area and Severity Index, the Investigators' Global Assessment and the pruritus score. The median exposure to pimecrolimus cream 1% was 22 treatment days (range, 9,29 treatment days). Pimecrolimus blood concentrations were <0.5 ng/mL in 94% of samples on day 1, in 93% of samples on day 10 and in 100% of samples on day 22, with no indication of an increase with increasing body surface area treated (up to 48% of the total body surface area). No drug-related systemic adverse events or serious adverse events were reported. Treatment was effective according to all efficacy parameters. The findings of this study indicate that the use of pimecrolimus cream 1% results in minimal systemic absorption of the active ingredient in pediatric patients of Japanese background with extensive disease. [source] Plasma concentrations of fluticasone propionate and budesonide following inhalation: effect of induced bronchoconstrictionBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2007Kevin J. Mortimer What is already known about this subject ,,All inhaled corticosteroids are absorbed into the systemic circulation and hence have the potential to cause adverse systemic effects. ,,Plasma drug concentrations following inhalation of 1000 µg fluticasone are considerably lower in people with airflow obstruction than in healthy volunteers but this is not the case for budesonide. What this study adds ,,This is the first study to determine whether changes in airflow obstruction within an individual affect the systemic absorption of inhaled fluticasone and budesonide; ,,Plasma concentrations of fluticasone and, to a lesser extent, those of budesonide were lower when the drugs were inhaled following induced bronchoconstriction; ,,The lower plasma concentrations of corticosteroids seen when the drugs were inhaled following induced bronchoconstriction is likely to reflect variations that will occur with fluctuations in airway caliber in asthma. Aims To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation. Methods Twenty people with mild asthma inhaled 1000 µg fluticasone (Accuhaler®) plus 800 µg budesonide (Turbohaler®) on two visits. On one occasion, prior to drug inhalation, FEV1 was decreased by at least 25% using inhaled methacholine. Plasma drug concentrations were measured for each drug over 5 h and area under the plasma concentration-time curve (AUC(0,5 h)) compared between visits. Results The mean difference in FEV1 prior to drug inhalation on the 2 days was 33%. AUC(0,5 h) values for fluticasone and budesonide were lower by a median of 60% (IQR 36,75) and 29% (IQR 2,44), respectively, when administered following bronchoconstriction; the reduction was greater for fluticasone than for budesonide, P = 0.007. Conclusions The lower plasma concentrations of fluticasone and, to a lesser extent, budesonide seen when the drugs were inhaled following induced bronchoconstriction, is likely to reflect variations that will occur with fluctuations in airway caliber in asthma. [source] Topical treatment of Netherton's syndrome with tacrolimus ointment without significant systemic absorptionBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2003G. Bens No abstract is available for this article. [source] | ||||||||||