Comparison of Therapeutic Effects and Safety of Once-daily versus Four-times-daily Intravenous Busulfan in Allogenic Transplantation

OBJECTIVE: To compare the therapeutic effects of the application of doxycycline-full dose (100 mg) and sub-dose (20 mg) in the treatment of periodontal disease.MATERIAL AND METHODS: A total of 60 patients with periodontal disease were examined. Patients are divided into two groups: A) treated with antimicrobial dose of 100 mg doxycycline once daily for 30 days, and B) treated with 2 x 20 mg/day. doxycycline, during 75 days. Among all patients a conservative treatment was carried out and ordinated the proper dose doxycycline in total dose during treatment from 3 gr. Index of dental plaque by Löe-Sillness, index of gingival inflammation and gingival bleeding by Cowell were followed.RESULTS: Values of dental plaque in relation first examination, 10th, 20th day, 1 month and 2.5 months, showed that after 2.5 months, average value (x = 0.83) of dental plaque in second group is slightly less than the value (x = 0.93) of dental plaque in the first group. The average value (x = 0.17) of gingival inflammation in second group is significantly less than the value (x = 0.50) of gingival inflammation in the first group. The average value (x = 0.97) of gingival bleeding in patients from the first group was significantly higher than value(x = 0.37) of gingival bleeding in the second group.CONCLUSION: Patients whose therapy was helped by a sub-dose doxycycline demonstrated positive therapeutic effects on gingival inflammation and bleeding.

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Age-Dependent Therapeutic Effects of Once-Daily Molsidomine Used as an Add-On Treatment in Patients with Stable Angina pectoris

Heart Drug ◽

10.1159/000082189 ◽

2004 ◽

Vol 4 (4) ◽

pp. 184-189 ◽

Cited By ~ 2

Author(s):

Roger Messin ◽

Fabienne Carreer-Bruhwyler ◽

Claude Dubois ◽

Jean-Pierre Famaey ◽

Joseph Géczy

Keyword(s):

Angina Pectoris ◽

Stable Angina ◽

Therapeutic Effects ◽

Stable Angina Pectoris ◽

Once Daily ◽

Age Dependent

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Safety and Effectiveness of Prophylactic Intravenous Itraconazole in Pediatric Stem Cell Transplantation Recipients.

Blood ◽

10.1182/blood.v110.11.4996.4996 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4996-4996

Author(s):

Chuhl Joo Lyu ◽

Sung Chul Won ◽

Seung-Hwan Oh ◽

Jung Woo Han ◽

Seung Yun Kwon ◽

...

Keyword(s):

Stem Cell ◽

Fungal Infection ◽

Liver Toxicity ◽

Trough Level ◽

Drug Level ◽

Cell Transplant ◽

Once Daily ◽

Level Change ◽

Allogenic Transplantation ◽

Trough Levels

Abstract Invasive fungal infections are a major cause of morbidity and mortality for childhood patients who underwent stem cell transplantations. Patients who underwent SCT have varying degree of gastrointestinal complications. In this study, invasive fungal infection prophylaxis with intravenous itraconazole (ITR) administration to pediatric patients with SCT was performed in order to evaluate effectiveness and safety. Prospective examination was performed between jan. 2006 and Feb. 2007. Total 30 patients were enrolled. Patient group was divided into autologous and allogenic transplantation due to cyclosporin-A (CsA) use in allogenic transplantation courses. ITR (2.5mg/kg/dose) was administered twice daily from D+1 to D+2. After D+2, once daily administration of ITR (2.5mg/kg/dose) was performed until D+16. Each group constitutes with 15 patients. Sampling was performed after 48 hours after initial administration of ITR. Sampling times were as follows: D+3 (0hr), D+4 (8hr, 19hr, 21hr, 24hr) after infusion of ITR administration for drug level change monitoring, and trough level monitoring for ITR at D+6, D+8, D+11, D+15, D+16. Blood plasma ITR and hydroxyl-itraconazole (OH-ITR) were measured by HPLC technique. CsA level also measured concomittantly. Any evidences for fungal infection, liver and kidney dysfunction were monitored. Mean trough concentrations of ITR were greater than prophylactic level (250 ng/mL), except 1st time (D+3, 0hr) level as 243.39 ± 172.19 in allogenic transplant group (figure). ITR and OH-ITR level were highter in autologous than allogenic group at D+4, 8hr (figure). Trough levels of ITR and OH-ITR for both allogenic and autologous group were not different statistically (figure). Trough level of CsA was 189.9 ± 43.9 ng/mL. Average reduction rate of CsA was 69% (30%–100%, no case for increasing dose) from starting dose. Figure. Itraconazole (A) and hydroxy-itraconazole (B) plasma levels in pediatric stem cell transplantation recipients. Figure One case of mortality due to sepsis (not due to fungal infection) was reported in allogenic transplantation group. No case of proven fungal infection during study period. There are no renal toxicities greater than grade I. Five patients of autologous transplantation group had liver toxicity more than grade I but no more than grade III. Allogenic transplantation group patients showed only 2 patients with liver toxicity of grade I. Prophylactic intravenous ITR for childhood stem cell transplant recipients showed stable trough levels for both autologous and allogenic transplantation conditions with acceptable toxicities. After achievement of trough level, drug level change showed that 8 hour level after infusion of ITR (maintain once daily dose) revealed most high level. CsA level showed stable, but dose should reduce to 69% of original amount. CsA level should be carefully monotored in case of concomittant use of ITR. Figure . / One case of mortality due to sepsis (not due to fungal infection) was reported in allogenic transplantation group. No case of proven fungal infection during study period. There are no renal toxicities greater than grade I. Five patients of autologous transplantation group had liver toxicity more than grade I but no more than grade III. Allogenic transplantation group patients showed only 2 patients with liver toxicity of grade I. Prophylactic intravenous ITR for childhood stem cell transplant recipients showed stable trough levels for both autologous and allogenic transplantation conditions with acceptable toxicities. After achievement of trough level, drug level change showed that 8 hour level after infusion of ITR (maintain once daily dose) revealed most high level. CsA level showed stable, but dose should reduce to 69% of original amount. CsA level should be carefully monotored in case of concomittant use of ITR.

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Exposure-Response Relationships for Efficacy and Safety of Filgotinib and its metabolite GS-829845 in Subjects with Rheumatoid Arthritis Based on Phase 2 and Phase 3 Studies

10.22541/au.162418885.56100410/v1 ◽

2021 ◽

Author(s):

Amy Meng ◽

Kacey Anderson ◽

Cara Nelson ◽

Liyun Ni ◽

Shu-Min Chuang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Pharmacokinetic Analysis ◽

Population Pharmacokinetic ◽

Therapeutic Effects ◽

Phase 2 ◽

Phase 3 ◽

Two Phase ◽

Once Daily ◽

Exposure Response ◽

Daily Dose

Aims:Filgotinib is a potent, oral, JAK1-preferential inhibitor for the treatment of rheumatoid arthritis (RA). This report describes exposure-response (ER) analyses of filgotinib for dose confirmation based on three Phase 3 and two Phase 2 studies in moderate to severe RA patients. Methods:The PK exposures used in ER analyses were derived from population pharmacokinetic analysis. The relationship between filgotinib exposures and various efficacy endpoints (ACR20/50/70 and DAS28) was assessed over octile groups of exposures by using combined exposures of filgotinib and GS-829845 (major, active metabolite). For the ER analyses of safety, exposures were examined between subjects who experienced and who did not experience the evaluated safety events, which was conducted separately for filgotinib and GS-829845. Results:Exposure efficacy relationships consistently revealed high response rates across the exposure range for filgotinib 200 mg once daily dose. A trend of increasing response with increasing exposure was observed over the exposure range for the primary and multiple secondary efficacy endpoints, with exposures associated with the 200 mg dose primarily residing on the curve plateau. For exposure-safety analyses, filgotinib and GS-829845 exposures were similar irrespective of presence/absence of the evaluated safety endpoints, indicating no exposure-safety relationship for common TEAEs, common laboratory abnormalities, serious TEAEs, or serious infections. Conclusions:ER analyses confirmed that filgotinib produced more robust therapeutic effects across the exposure range observed at 200 mg once daily compared to lower doses. The positive exposure-efficacy relationship and a lack of exposure-safety relationship on the evaluated safety endpoints supported the 200 mg once daily dose for commercialization.

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RgIA4 Accelerates Recovery from Paclitaxel-Induced Neuropathic Pain in Rats

Marine Drugs ◽

10.3390/md18010012 ◽

2019 ◽

Vol 18 (1) ◽

pp. 12 ◽

Cited By ~ 2

Author(s):

Peter N. Huynh ◽

Denise Giuvelis ◽

Sean Christensen ◽

Kerry L. Tucker ◽

J. Michael McIntosh

Keyword(s):

Neuropathic Pain ◽

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Therapeutic Effects ◽

Chemotherapeutic Drugs ◽

Chemotherapeutic Drug ◽

Sprague Dawley ◽

Once Daily ◽

Sprague Dawley Rats ◽

Rescue Mechanism

Chemotherapeutic drugs are widely utilized in the treatment of human cancers. Painful chemotherapy-induced neuropathy is a common, debilitating, and dose-limiting side effect for which there is currently no effective treatment. Previous studies have demonstrated the potential utility of peptides from the marine snail from the genus Conus for the treatment of neuropathic pain. α-Conotoxin RgIA and a potent analog, RgIA4, have previously been shown to prevent the development of neuropathy resulting from the administration of oxaliplatin, a platinum-based antineoplastic drug. Here, we have examined its efficacy against paclitaxel, a chemotherapeutic drug that works by a mechanism of action distinct from that of oxaliplatin. Paclitaxel was administered at 2 mg/kg (intraperitoneally (IP)) every other day for a total of 8 mg/kg. Sprague Dawley rats that were co-administered RgIA4 at 80 µg/kg (subcutaneously (SC)) once daily, five times per week, for three weeks showed significant recovery from mechanical allodynia by day 31. Notably, the therapeutic effects reached significance 12 days after the last administration of RgIA4, which is suggestive of a rescue mechanism. These findings support the effects of RgIA4 in multiple chemotherapeutic models and the investigation of α9α10 nicotinic acetylcholine receptors (nAChRs) as a non-opioid target in the treatment of chronic pain.

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Therapeutic effects of alendronate 35 mg once weekly and 5 mg once daily in Japanese patients with osteoporosis: a double-blind, randomized study

Journal of Bone and Mineral Metabolism ◽

10.1007/s00774-005-0616-5 ◽

2005 ◽

Vol 23 (5) ◽

pp. 382-388 ◽

Cited By ~ 48

Author(s):

Shinji Uchida ◽

Tadaaki Taniguchi ◽

Takafumi Shimizu ◽

Taro Kakikawa ◽

Kotoba Okuyama ◽

...

Keyword(s):

Randomized Study ◽

Japanese Patients ◽

Therapeutic Effects ◽

Double Blind ◽

Once Daily

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Melatonin Potentiates the Therapeutic Effects of Metformin in Women with Metabolic Syndrome

Scientia Pharmaceutica ◽

10.3390/scipharm88020028 ◽

2020 ◽

Vol 88 (2) ◽

pp. 28

Author(s):

Sattar J. Abood ◽

Waleed K. Abdulsahib ◽

Saad A. Hussain ◽

Sajida H. Ismail

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Lipid Profile ◽

Treatment Protocol ◽

International Diabetes Federation ◽

Controlled Study ◽

Controlled Clinical Trial ◽

Therapeutic Effects ◽

Double Blind ◽

Once Daily

Objective: This study evaluated the effect of melatonin on the response of patients suffering from metabolic syndrome (MEBS) treated with metformin. Design: This study used two-armed groups in a double-blind, randomized controlled clinical trial. Materials and Methods: A randomized double-blind placebo-controlled study was carried out on female patients diagnosed as having MEBS, according to the International Diabetes Federation (IDF) diagnosing criteria of MEBS (2005), from the outpatient clinic in Al-Zahraa Teaching Hospital/Kut, Iraq. They were diagnosed utilizing laboratory and clinical investigations, then randomized into two groups. The first group (group A) was treated with metformin (500 mg) twice daily, in addition to a placebo formula once daily at bedtime for three months. The second group (group B) was treated with metformin (500 mg) twice daily after meals, in addition to melatonin (10 mg) once daily at bedtime for three months. Results: The treatment of patients with MEBS using metformin–melatonin showed an improvement in most MEBS components such as fasting serum glucose (FSG), lipid profile, and body mass index (BMI), in addition to a reduction in insulin resistance and hyperinsulinemia. Simultaneously, there were increments in serum uric acid (UA), leptin, prolactin (PRL), and estradiol levels, while serum progesterone level decreased. Furthermore, patients treated with metformin–placebo showed less improvement in the studied parameters compared to that produced due to the inclusion of melatonin in the treatment protocol. Conclusion: Melatonin improves the effect of metformin on several components of MEBS such as FSG, lipid profile, and BMI, in addition to insulin resistance and hyperinsulinemia, compared to metformin alone.

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Hyperbaric oxygen: a novel modality to ameliorate experimental colitis

Gut ◽

10.1136/gut.43.4.512 ◽

1998 ◽

Vol 43 (4) ◽

pp. 512-518 ◽

Cited By ~ 36

Author(s):

D Rachmilewitz ◽

F Karmeli ◽

E Okon ◽

I Rubenstein ◽

O S Better

Keyword(s):

Inflammatory Bowel Disease ◽

Acetic Acid ◽

Hyperbaric Oxygen ◽

Bowel Disease ◽

Experimental Colitis ◽

Prostaglandin E ◽

Therapeutic Effects ◽

Once Daily ◽

Inflammatory Bowel

Background—Hyperbaric oxygen (HBO) has been suggested to be beneficial in inflammatory bowel disease but the mechanisms responsible for its therapeutic effects have not been elucidated.Aim—To assess the effect of HBO treatment on colonic damage in two models of experimental colitis, and to examine whether this effect is mediated by modulation of NO synthesis.Methods—Colitis was induced by either flushing the colon with 2 ml 5% acetic acid or intracolonic administration of 30 mg trinitrobenzenesulphonic acid (TNB) dissolved in 0.25 ml 50% ethanol. Rats were exposed to HBO (100% oxygen at 2.4 atmosphere absolute) for one hour twice on the day of colitis induction and once daily thereafter. Control rats were treated only with acetic acid or TNB. Rats were killed 24 hours after acetic acid administration or one and seven days after TNB treatment. The colon was isolated, washed, and weighed, the lesion area was measured, and mucosal scrapings were processed for determination of myeloperoxidase (MPO) and NO synthase (NOS) activities, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) generation.Results—In control rats exposed for seven days to HBO, colonic NOS activity was significantly decreased by 61%, compared with its activity in untreated rats (2.93 (0.17) nmol/g/min). HBO significantly reduced by 51 and 62% the extent of injury induced by acetic acid and TNB respectively. The protection provided by HBO was accompanied by a significant decrease in colonic weight, PGE2 generation, MPO, and NOS activities. In acetic acid colitis, LTB4 generation was also significantly decreased.Conclusions—(1) HBO effectively decreases colitis induced by acetic acid and TNB. (2) The decreased NOS activity induced by HBO suggests that reduction in NO generation may be among the mechanisms responsible for the anti-inflammatory effect of HBO. (3) HBO may be considered in the treatment of patients with refractory inflammatory bowel disease.

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SCO-267, a GPR40 Full Agonist, Stimulates Islet and Gut Hormone Secretion and Improves Glycemic Control in Humans

10.2337/figshare.15036009.v1 ◽

2021 ◽

Author(s):

Harunobu Nishizaki ◽

Osamu Matsuoka ◽

Tomoya Kagawa ◽

Akihiro Kobayashi ◽

Masanori Watanabe ◽

...

Keyword(s):

Glycemic Control ◽

Healthy Adults ◽

Oral Glucose ◽

Therapeutic Effects ◽

Clinical Effects ◽

Dependent Manner ◽

Once Daily ◽

Full Agonist ◽

Gut Hormone ◽

Patients With Diabetes

SCO-267 is a full agonist of the free fatty acid receptor 1 (GPR40), which regulates the secretion of islet and gut hormones. In this phase 1 study, we aimed to evaluate the clinical profile of single and multiple once-daily oral administration of SCO-267 in healthy adults and patients with diabetes. Plasma SCO-267 concentration was seen to increase in a dose-dependent manner after administration, and its plasma exposure was maintained for 24 h. Repeated dose did not alter the pharmacokinetic profile of SCO-267 in healthy adults. SCO-267 was generally safe and well tolerated at all evaluated single and multiple doses. Single and repeated doses of SCO-267 stimulated the secretion of insulin, glucagon, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and peptide YY in healthy adults. Furthermore, a single dose of SCO-267 stimulated the secretion of these hormones, decreased fasting hyperglycemia, and improved glycemic control during an oral glucose tolerance test in patients with diabetes, without inducing hypoglycemia. This study is the first to demonstrate the clinical effects of a GPR40 full agonist. SCO-267 is safe and well tolerated and exhibits once-daily oral dosing potential. Its robust therapeutic effects on hormonal secretion and glycemic control make SCO-267 an attractive drug candidate for the treatment of diabetes.

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SCO-267, a GPR40 Full Agonist, Stimulates Islet and Gut Hormone Secretion and Improves Glycemic Control in Humans

10.2337/figshare.15036009 ◽

2021 ◽

Author(s):

Harunobu Nishizaki ◽

Osamu Matsuoka ◽

Tomoya Kagawa ◽

Akihiro Kobayashi ◽

Masanori Watanabe ◽

...

Keyword(s):

Glycemic Control ◽

Healthy Adults ◽

Oral Glucose ◽

Therapeutic Effects ◽

Clinical Effects ◽

Dependent Manner ◽

Once Daily ◽

Full Agonist ◽

Gut Hormone ◽

Patients With Diabetes

SCO-267 is a full agonist of the free fatty acid receptor 1 (GPR40), which regulates the secretion of islet and gut hormones. In this phase 1 study, we aimed to evaluate the clinical profile of single and multiple once-daily oral administration of SCO-267 in healthy adults and patients with diabetes. Plasma SCO-267 concentration was seen to increase in a dose-dependent manner after administration, and its plasma exposure was maintained for 24 h. Repeated dose did not alter the pharmacokinetic profile of SCO-267 in healthy adults. SCO-267 was generally safe and well tolerated at all evaluated single and multiple doses. Single and repeated doses of SCO-267 stimulated the secretion of insulin, glucagon, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and peptide YY in healthy adults. Furthermore, a single dose of SCO-267 stimulated the secretion of these hormones, decreased fasting hyperglycemia, and improved glycemic control during an oral glucose tolerance test in patients with diabetes, without inducing hypoglycemia. This study is the first to demonstrate the clinical effects of a GPR40 full agonist. SCO-267 is safe and well tolerated and exhibits once-daily oral dosing potential. Its robust therapeutic effects on hormonal secretion and glycemic control make SCO-267 an attractive drug candidate for the treatment of diabetes.

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