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Single Oral (single + oral)
Terms modified by Single Oral Selected AbstractsHead regeneration in HydraDEVELOPMENTAL DYNAMICS, Issue 2 2003Hans R. Bode Abstract Hydra, a primitive metazoan, has a simple structure consisting of a head, body column, and foot aligned along a single oral,aboral axis. The body column has a high capacity for regeneration of both the head and foot. Because of the tissue dynamics that take place in adult Hydra, the processes governing axial patterning are continuously active to maintain the form of the animal. Regeneration in hydra is morphallactic and closely related to these axial patterning processes. As might be expected, analysis at the molecular level indicates that the same set of genes are involved in head regeneration and the maintenance of the head in the context of the tissue dynamics of the adult. The genes analyzed so far play roles in axial patterning processes in bilaterians. Developmental Dynamics 226:225,236, 2003. © 2003 Wiley-Liss, Inc. [source] Effect of lesogaberan, a novel GABAB -receptor agonist, on transient lower oesophageal sphincter relaxations in male subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2010G. E. BOECKXSTAENS Aliment Pharmacol Ther,31, 1208,1217 Summary Background, Transient lower oesophageal sphincter relaxations (TLESRs) are a major mechanism behind gastro-oesophageal reflux disease (GERD). Aim, To assess the effect of lesogaberan (AZD3355) , a novel peripherally active GABAB receptor agonist , on TLESRs. Methods, Twenty-four healthy men were enrolled in this single-blind, placebo-controlled, randomized, single-centre, three-period crossover phase 1 study. Subjects were randomized to receive single oral doses of lesogaberan (0.8 mg/kg), baclofen (40 mg) and placebo, separated by washout periods of ,7 days. Subjects finished a meal 1 h after the dose. Oesophageal manometry and pH-metry measurements were taken during the 3 h after the meal. Results, Twenty-one subjects completed the study. Compared with placebo, lesogaberan 0.8 mg/kg significantly reduced the number of TLESRs by 36% [geometric mean ratio (GMR): 0.64; 95% confidence interval (CI): 0.51,0.82] and significantly reduced the number of acid reflux episodes (mean reduction: 1.6; 95% CI: 0.34,2.9). Lesogaberan also significantly increased lower oesophageal sphincter (LES) pressure by 39% compared with placebo (GMR: 1.39; 95% CI: 1.18,1.64). Comparable results were observed with baclofen. Similar numbers of adverse events were reported by subjects taking lesogaberan and placebo. Conclusion, Compared with placebo, lesogaberan significantly reduced TLESRs and acid reflux episodes and increased LES pressure. [source] The GABAB receptor agonist AZD9343 inhibits transient lower oesophageal sphincter relaxations and acid reflux in healthy volunteers: a phase I studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009H. BEAUMONT Summary Background, Transient lower oesophageal sphincter relaxations (TLESRs) represent an interesting target for the treatment of gastro-oesophageal reflux. Baclofen reduces TLESRs and reflux episodes, but is not optimal for clinical application because of its central side effects. Therefore, new agents are required. Aim, To study the effect of AZD9343, a new selective GABAB receptor agonist, in healthy volunteers. Methods, A total of 27 subjects participated in a placebo-controlled, randomized, two-centre phase I study. Subjects underwent oesophageal manometry and pH-metry for 3 h postprandially. Before meal ingestion, a single oral dose of placebo, 60 and 320 mg AZD9343 or 40 mg baclofen was given on four separate days. Results, Somnolence was reported after 320 mg AZD9343 and baclofen. Reversible short-lasting paraesthesia was reported after AZD9343. AZD9343 320 mg and baclofen significantly reduced the number of TLESRs with 32% and 40% respectively. Acid reflux was significantly decreased by AZD9343 and baclofen. Like baclofen, AZD9343 increased LES pressure before meal intake. AZD9343 320 mg and baclofen significantly reduced the swallowing rate. Conclusions, Like baclofen, AZD9343 dose-dependently decreases the number of TLESRs and acid reflux episodes, increases LES pressure and reduces swallowing, extending the concept that GABAB agonists are potent reflux inhibitors. However, discovery of analogues with an improved side effect profile is warranted. [source] 5-aminosalicylic acid release from a new controlled-release mesalazine formulation during gastrointestinal transit in healthy volunteersALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2006M. BRUNNER Summary Background Mesalazine (5-aminosalicylic acid, 5-ASA) containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. A novel formulation with an Eudragit L/S mixture coating has been developed to provide selective release of 5-ASA to the ileo-caecal region and the colon. Aim To determine the release of 5-ASA during the gastrointestinal transit. Methods A single oral dose of mesalazine EC 500 mg gastroresistant tablets (Asamax) was administered to eight healthy male volunteers. Gastrointestinal transit and tablet disintegration were monitored by scintigraphy. 5-ASA release was verified by assessing plasma pharmacokinetics. Results Initial tablet disintegration was observed 5.65 ± 0.86 h after dosing, corresponding to the detection of 5-ASA in plasma. This occurred in the ileo-caecal region in three subjects and the ascending colon in the remaining five. The relative percentage of 5-ASA absorption was more pronounced in the ascending colon (41 ± 27.4%) than the ileo-caecal region (6.6 ± 9.2%). Conclusion This mesalazine EC gastroresistant tablets release locally active 5-ASA specifically in the ileo-caecal region and the ascending colon. [source] Simultaneous determination of the flavonoid aglycones diosmetin and hesperetin in human plasma and urine by a validated GC/MS method: in vivo metabolic reduction of diosmetin to hesperetinBIOMEDICAL CHROMATOGRAPHY, Issue 2 2009Marios Spanakis Abstract Diosmetin and hesperetin are the aglycones of the flavonoid glycosides diosmin and hesperidin which occur naturally in citrus fruit. A GC/MS method for the simultaneous determination of diosmetin and hesperetin in human plasma and urine has been developed and validated. The method was linear in the 2,300 ng/mL concentration range for both diosmetin and hesperetin in plasma and urine (r >0.999). The precision of the method was better than 6.01 and 7.16% for diosmetin and hesperetin, respectively, and the accuracy was 96.76,100.40% and 95.00,105.50% for diosmetin and hesperetin, respectively. The lower limit of quantitation was found to be 2 ng/mL for both analytes in plasma and urine. Recovery of diosmetin, hesperetin and internal standard naringenin was greater than 82.5%. The method has been applied for the determination of diosmetin and hesperetin in plasma and urine samples obtained from a healthy male subject following a single oral 1000 mg dose of the flavonoid glycoside diosmin. The presence of hesperetin in plasma and urine samples indicates the metabolic reduction of diosmetin to its flavanone analogue hesperetin through reduction of the 2,3 double bond of the C-ring by the enzymes of bacteria of the intestinal microflora. Copyright © 2008 John Wiley & Sons, Ltd. [source] Pharmacokinetic and pharmacodynamic study of morphine and morphine 6-glucuronide after oral and intravenous administration of morphine in children with cancerBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2009Simin O. Mashayekhi Abstract The aim of this study was to characterize the pharmacokinetics and pharmacodynamics of morphine and morphine 6-glucuronide (M6G) in children with cancer. Serum concentrations of morphine and M6G in children who received single oral or short term continuous intravenous morphine were determined by HPLC and ELISA assays, respectively. The serum Cmax of morphine and M6G after i.v. morphine administration was 560.5 and 309.0,nM and the Tmax was 61 and 65,min, respectively. The elimination half-life was 140.0 and 328.7,min, respectively. After oral administration of morphine, the serum Cmax of morphine and M6G was 408.34 and 256.3,nM and the Tmax was 40.0 and 60,min, respectively. The half-life was 131.0 and 325.8,min, respectively. The side effects were: drowsiness (100%), nausea and/or vomiting (57%), pruritus (28%) and urinary retention (14%). There were no reports of respiratory complications. This study showed that pharmacokinetics factors of morphine and M6G in children were significantly different from adults. Therefore the required dose for children should be different from that of adults and should be based on studies performed on children rather than on studies on adults. Some adverse effects, particularly nausea and pruritus, may be commoner than is usually thought, while others, particularly respiratory problems did not occur. Copyright © 2009 John Wiley & Sons, Ltd. [source] Pharmacokinetics of E-6087, a new anti-inflammatory agent, in rats and dogsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2001Raquel F. Reinoso Abstract The pharmacokinetics of E-6087, a newly developed cyclooxygenase-2 inhibitor, was studied in rats and dogs after single oral and intravenous doses. In both animal species, E-6087 was characterized by a long elimination half-life (20,35 h), a low plasma clearance (0.10,0.22 l h,1 kg,1) and a relatively large volume of distribution (2,6 l kg,1). Oral bioavailability was lower in dogs than in rats whereas a faster elimination was found in rats. Multiple peaks were present regardless of administration route and animal species, suggesting the existence of enterohepatic circulation. Gender effect on the pharmacokinetics of E-6087 was only found in rats, with greater exposure and longer elimination in females than in males. Food intake reduced the bioavailability (,22%) with no apparent changes in the absorption rate. After oral dosing of 1, 5 and 25 mg kg,1 to rats, linearity was lost at the highest dose due to the low aqueous solubility of E-6087. Drug absorption was improved by micronization. E-6087 and E-6132, (a pharmacologically active metabolite), showed different pharmacokinetics. The higher percentage of E-6087 at early times suggests that E-6087 is the main compound responsible for in vivo activity, although E-6132 would contribute to the activity at later times. Copyright © 2001 John Wiley & Sons, Ltd. [source] The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteersBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2008Yan-Ling He What is already known about this subject ,,Vildagliptin is a new, potent, and selective inhibitor of DPP-4. ,,The efficacy and safety of vildagliptin in type 2 diabetes has been intensively studied in diverse subject populations. ,,There has been little information published about the pharmacokinetics and pharmacodynamics of vildagliptin. What this study adds ,,No clinically relevant changes in pharmacokinetics or pharmacodynamics were observed between young and elderly, male and female, or high body mass index (BMI) and low BMI subjects. ,,The results suggest that no dose modification is necessary for vildagliptin based on the age, gender, or BMI of a subject. Aims To evaluate the effect of age, gender, and body mass index (BMI) on the pharmacokinetics and pharmacodynamics of vildagliptin. Methods Forty healthy subjects received a single oral dose of 100 mg vildagliptin to assess the effects of age, gender, and BMI on the pharmacokinetics and pharmacodynamics, reflected by the time course of inhibition of DPP-4 activity, of vildagliptin. Results Peak concentration and exposure (AUC(0,,)) of vildagliptin were 17% (90% CI 2, 35%) and 31% (90% CI 18, 45%) higher in elderly vs. young subjects. Renal clearance was reduced by 32% (90% CI 17, 45%) in elderly subjects. The pharmacokinetics of vildagliptin were not significantly influenced by gender or BMI. Inhibition of DPP-4 activity was similar regardless of age, gender, or BMI. Conclusions The pharmacokinetics of a single oral 100 mg dose of vildagliptin were not affected by gender and BMI. Exposure to vildagliptin was higher in elderly patients, but this was not associated with any difference in the effect of DPP-4 inhibition. Based on these results, no vildagliptin dose adjustment is necessary for age, gender, or BMI. [source] The effects of ritonavir and lopinavir/ritonavir on the pharmacokinetics of a novel CCR5 antagonist, aplaviroc, in healthy subjectsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2006Kimberly K. Adkison Aims This study assessed the effects of the CYP3A inhibitors lopinavir/ritonavir (LPV/r) on the steady-state pharmacokinetics (PK) of aplaviroc (APL), a CYP3A4 substrate, in healthy subjects. Methods In Part 1, APL PK was determined in eight subjects who received a single oral 50-mg APL test dose with/without a single dose of 100 mg ritonavir (RTV). Part 2 was conducted as an open-label, single-sequence, three-period repeat dose study in a cohort of 24 subjects. Subjects received APL 400 mg every 12 h (b.i.d.) for 7 days (Period 1), LPV/r 400/100 mg b.i.d. for 14 days (Period 2) and APL 400 mg +,LPV/r 400/100 mg b.i.d. for 7 days (Period 3). All doses were administered with a moderate fat meal. PK sampling occurred on day 7 of Periods 1 and 3 and day 14 of Period 2. Results In Part 1, a single RTV dose increased the APL AUC0,, by 2.1-fold [90% confidence interval (CI) 1.9, 2.4]. Repeat dose coadministration of APL with LPV/r increased APL exposures to a greater extent with the geometric least squares mean ratios (90% CI) being 7.7 (6.4, 9.3), 6.2 (4.8, 8.1) and 7.1 (5.6, 9.0) for the APL AUC, Cmax, and Cmin, respectively. No change in LPV AUC or Cmax and a small increase in RTV AUC and Cmax (28% and 32%) were observed. The combination of APL and LPV/r was well tolerated and adverse events were mild in severity with self-limiting gastrointestinal complaints most commonly reported. Conclusions Coadministration of APL and LPV/r was well tolerated and resulted in significantly increased APL plasma concentrations. [source] Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionalityBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2002Donald J. Nichols Aims, To determine the absolute bioavailability, dose proportionality and the effects of food on the pharmacokinetics of single oral doses of sildenafil citrate. Methods, Three open-label, randomized crossover studies were conducted in healthy male subjects. Absolute bioavailability was determined by comparing pharmacokinetic data after administration of single oral and intravenous 50-mg doses of sildenafil (n=12 subjects). Food effects were examined by comparing pharmacokinetic data for sildenafil and its primary circulating metabolite, UK-103,320, after administration of a single oral 100-mg dose in the fasted and fed states (n=34 subjects). Dose proportionality was assessed from pharmacokinetic data obtained after administration of four single oral doses of sildenafil (25, 50, 100 and 200 mg) to 32 subjects. The safety and tolerability of sildenafil were also assessed in all of these studies. Results, The calculated absolute oral bioavailability of sildenafil was 41% (90% CI: 36,47). Food slowed the rate of absorption, delaying mean tmax by approximately 1 h and reducing Cmax by 29% (90% CI: 19,38). Systemic exposure, as assessed by the mean area under the plasma concentration,time curve (AUC), was reduced by 11% (90% CI: 6,16). These food effects were not considered to be of clinical significance. There was statistical evidence of nonproportionality in Cmax and AUC over the dose range 25,200 mg. However the degree of nonproportionality was small, with predicted increases in Cmax and AUC of 2.2- and 2.1-fold, respectively, for a doubling in dose, and was thought to be clinically nonsignificant. Sildenafil was well tolerated in the three studies; the majority of adverse events were mild and transient. Conclusions, Sildenafil had a mean absolute bioavailability of 41%. Food caused small reductions in the rate and extent of systemic exposure; these reductions are unlikely to be of clinical significance. Across the dose range of 25,200 mg, systemic exposure increased in a slightly greater than dose-proportional manner. [source] Correlation between R/S enantiomer ratio of lansoprazole and CYP2C19 activity after single oral and enteral administrationCHIRALITY, Issue 7 2010Masatomo Miura Abstract The purpose of this study was to investigate whether CYP2C19 activity can be estimated from plasma concentrations of lansoprazole enantiomers 4 h (C4h) after single administration by oral and enteral routes. Sixty-nine subjects, 22 homozygous extensive metabolizers (homEMs), 32 heterozygous EMs (hetEMs), and 15 poor metabolizers (PMs), participated in the study. After a single oral or enteral dose of racemic lansoprazole (30 mg), plasma concentrations of lansoprazole enantiomers were measured 4 h postdose. The R/S ratio of lansoprazole at 4 h differed significantly among the three groups (P < 0.0001) regardless of the administration route. The R/S ratio of lansoprazole in CYP2C19 PMs ranged from 3.0 to 13.7, whereas in homEMs and hetEMs the ratio ranged from 8.6 to 90 and 2.1 to 122, respectively. The relationship between (S)-lansoprazole concentration and R/S ratio of lansoprazole at C4h is given by the following formula: log10 [R/S ratio] = 2.2 , 0.64 × log10 [C4h of (S)-lansoprazole] (r = 0.867, P < 0.0001). Thus, phenotyping CYP2C19 using the R/S enantiomer ratio of lansoprazole seems unlikely. However, to obtain a pharmacological effect similar to that in CYP2C19 PMs, we can presume that lansoprazole has a sufficient effect in the patient with an R/S enantiomer ratio at 4 h , 13.70 and (S)-lansoprazole concentration at 4 h , 50 ng/ml. Chirality 2010. © 2009 Wiley-Liss, Inc. [source] Single-dose extended-release oral azithromycin vs.CLINICAL MICROBIOLOGY AND INFECTION, Issue 12 2009-haemolytic streptococcal pharyngitis/tonsillitis in adults, 3-day azithromycin for the treatment of group A, adolescents: a double-blind, double-dummy study Abstract The azithromycin immediate-release formulation (AZ-IR) provides effective treatment for group A ,-haemolytic streptococcal pharyngitis in adults. Single-dose therapy with a novel azithromycin extended-release (AZ-ER) formulation could reduce treatment failure and eliminate non-compliance contributing to antimicrobial resistance. A randomized, double-blind, double-dummy, multicentre trial was conducted comparing AZ-ER (single oral 2-g dose) with AZ-IR (3 days, 500 mg once daily) for the treatment of group A ,-haemolytic streptococcal pharyngitis/tonsillitis in adults and adolescents (n = 598). The primary endpoint was bacteriological eradication at test -of-cure (TOC; day 24,28) in the bacteriological per-protocol population (n = 420). Bacteriological eradication was achieved in 85.4% (175/205) and 81.4% (175/215) of subjects in the AZ-ER and AZ-IR groups, respectively (95% CI ,3.1,11.1). Clinical cure at TOC occurred in 99.0% of subjects in the AZ-ER group and in 96.7% in the AZ-IR group. At long-term follow-up, bacteriological recurrence was observed in 5.5% (9/163) and 7.7% (12/156), respectively. Both treatments were well tolerated; and most adverse events (AEs) were mild to moderate in intensity. The most frequent treatment-related AE was diarrhoea, or loose stools, in 11% of both treatment groups. AZ-ER-treated and AZ-IR-treated subjects had AE burdens (AE days/patient-year) of 7.6 days and 9.2 days, respectively. A similar trend in favour of AZ-ER was noted for treatment-related diarrhoea burden (1.9 days vs. 2.5 days). A single 2-g dose of AZ-ER is as effective and well tolerated as 3 days of AZ-IR (500 mg once daily) for treating group A ,-haemolytic streptococcal pharyngitis/tonsillitis in adults and adolescents. [source] | |||||||||||||