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Mean Ratio (mean + ratio)

Distribution by Scientific Domains
Medical Sciences82%
Life Sciences11%
Distribution within Medical Sciences
Allergy & Clinical Immunology13%

Kinds of Mean Ratio

  • geometric mean ratio
    		•

    Selected Abstracts

    The relationship between tiller appearance in spring and contribution to dry-matter yield in perennial ryegrass (Lolium perenne L.) cultivars differing in heading date

    GRASS & FORAGE SCIENCE, Issue 2 2005
    A. S. Laidlaw
    Abstract The relative contribution of tillers present in April and those appearing in consecutive periods in spring was assessed for perennial ryegrass cultivars in the three maturity groups (early, intermediate- and late-heading). Each group was represented by two diploid and one tetraploid cultivar each in plots in their third (2000) and fourth (2001) harvest years in three replicated blocks receiving an average of 325 kg N ha,1 and cut seven (in 2001) or eight (in 2000) times annually. ,Main' tillers and their daughters were marked with colour-coded PVC-covered wire loops in early April as were daughters which appeared in consecutive periods between harvests, the loop colour identifying the period of origin of the tiller. Tillers were harvested at cutting height (5 cm) before the plots were harvested and the herbage from tillers with the same colour code bulked per plot. Tillers were identified retrospectively as ,reproductive' if they had been decapitated at the previous harvest. Dry-matter yield was higher in the early than late-heading cultivars in April and early May but this was reversed in harvests in late May and June. The early heading group had a lower lamina content than the late-heading group during reproduction growth, both due to the reproductive tillers (mainly those which overwintered) having a lower leaf content and to their being fewer and smaller vegetative tillers during the reproductive phase than for the late-heading group. Turnover of tillers was high in spring due to decapitation of reproductive tillers and rapid post-flowering tillering. This was particularly pronounced in the early heading group which also had slightly more tillers marked in April which were subsequently decapitated than in the other maturity groups, i.e. 0·56 compared with 0·44 for the late-maturing group. Mean ratios of rate of death: rate of tillering for 3 years (1999,2001) for the early and late-heading groups were 0·8 and 0·4, respectively, for April,May and 1·1 and 2·4, respectively, for June indicating the different patterns in tiller turnover for the two extreme maturity groups. Information on tiller origin and contribution to yield can be used to refine tiller-based grass growth models. [source]

    Is there a greater mandibular movement capacity towards the left?

    JOURNAL OF ORAL REHABILITATION, Issue 4 2005
    Verification of an observation from 192
    summary, In 1921, the German dentist Hans Wertheim reported that more individuals were able to shift the mandible more towards the left than to the right. This study analyses the deviation from symmetrical mobility of the lower jaw in either direction. Using a millimetre ruler, maximum jaw opening (MJO), maximum left laterotrusion (MLL), and maximum right laterotrusion (MRL) were recorded in 141 healthy individuals and in 141 patients with temporomandibular disorders (TMDs). For both sexes, the mean maximum movements to the left and to the right were greater in the healthy group as compared with the TMD group. Healthy subjects as well as patients were able to move the mandible more to one side. Only a minority had identical values for MLL and MRL. The majority of healthy individuals and TMD patients could move more to the left (P < 0·001). In the healthy group, the mean ratio between MJO and MLL was 5·0, and 5·5 between MJO and MRL. In the TMD group, the corresponding values were 4·6 and 6.1. The mean absolute difference between MLL and MLR (in mm) was 1·24 [95% confidence interval (CI): 0·99; 1·49] among healthy females, and 2·09 (95% CI: 1·52; 2·66) among healthy males. In the TMD group, the corresponding values were 2·62 (95% CI: 2·21; 3·04) and 2·83 (95% CI: 1·67; 4·00), respectively. From the results of our study we conclude that moderate deviations from symmetric movements (mean: 1·2 mm for women, 2·1 mm for men) appear to be the norm even in healthy individuals. [source]

    Quantitative study of bite force during sleep associated bruxism

    JOURNAL OF ORAL REHABILITATION, Issue 5 2001
    K. Nishigawa
    Nocturnal bite force during sleep associated bruxism was measured in 10 subjects. Hard acrylic dental appliances were fabricated for the upper and lower dentitions of each subject. Miniature strain-gauge transducers were mounted to the upper dental appliance at the right and left first molar regions. In addition, thin metal plates that contact the strain-gauge transducers were attached to the lower dental appliance. After a 1-week familiarization with the appliances, nocturnal bite force was measured for three nights at the home of each subject. From the 30 recordings, 499 bruxism events that met the definition criteria were selected. The above described system was also used to measure the maximum voluntary bite forces during the daytime. The mean amplitude of detected bruxism events was 22·5 kgf (s.d. 13·0 kgf) and the mean duration was 7·1 s (s.d. 5·3 s). The highest amplitude of nocturnal bite force in individual subjects was 42·3 kgf (15·6,81·2 kgf). Maximum voluntary bite force during the daytime was 79·0 kgf (51·8,99·7 kgf) and the mean ratio of nocturnal/daytime maximum bite force was 53·1% (17·3,111·6%). These data indicate that nocturnal bite force during bruxism can exceed the amplitude of maximum voluntary bite force during the daytime. [source]

    Effect of lesogaberan, a novel GABAB -receptor agonist, on transient lower oesophageal sphincter relaxations in male subjects

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2010
    G. 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]

    Exhaled nitric oxide in asthmatic and non-asthmatic children: Influence of type of allergen sensitization and exposure to tobacco smoke

    PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 5 2001
    Mario Barreto
    Asthmatic bronchial inflammation is associated with increased nitric oxide concentrations in exhaled air (eNO). Recent data suggest that this effect arises from atopy. Our aim in this study was to find out whether atopy and sensitization to particular allergens influences eNO levels. A total of 213 subjects (41 asthmatics and 172 controls) (96 boys and 117 girls, 7.3,14 years of age) were studied. Parents completed a questionnaire that sought information on their children's respiratory symptoms and exposure to tobacco smoke. Subjects underwent skin-prick tests for the following common allergens: Dermatophagoides pteronyssinus (Dpt), cat fur, Aspergillus fumigatus, Alternaria tenuis, mixed grass, mixed tree pollen, Parietaria officinalis, egg, and cow's milk. eNO was collected in 1-l mylar bags (exhaled pressure 10 cmH2O, flow 58 ml/s) and analyzed by using chemiluminescence. Atopic and non-atopic children without a history of chronic respiratory symptoms had a similar geometric mean eNO (atopics, n = 28, 11.2 p.p.b.; non-atopics, n = 96, 10.0 p.p.b.; mean ratio 1.1, 95% confidence interval [CI]: 0.7,1.6). Conversely, atopic asthmatic subjects had significantly higher eNO values than non-atopic asthmatic subjects (atopics, n = 25, 24.8 p.p.b.; non-atopics, n = 16, 11.4 p.p.b.; mean ratio 2.2, 95% CI: 1.2,3.9, p=,0.000). In children with rhinitis alone (n = 15) and those with lower respiratory symptoms other than asthma (n = 33), eNO increased slightly, but not significantly, with atopy. eNO levels correlated significantly with Dpt wheal size (r = 0.51) as well with the wheal size for cat, mixed grass, and Parietaria officinalis (r = 0.30,0.29), and with the sum of all wheals (r = 0.47) (p=,0.000). Subjects sensitized only for Dpt (but not those subjects sensitized only for grass pollen or other allergens) showed significantly higher eNO levels than non-atopic subjects (16.4 p.p.b. vs. 10.2 p.p.b., mean ratio 1.6, 95% CI: 1.1,2.3, p=,0.002). In asthmatic subjects, Dpt sensitization markedly increased eNO levels (Dpt- sensitized subjects: 28.0 p.p.b.; Dpt- unsensitized subjects: 12.2 p.p.b.; mean ratio 2.3, 95% CI: 1.5,3.5, p=,0.000). Non-asthmatic Dpt- sensitized subjects also had significantly higher eNO values than non-asthmatic, non- Dpt -sensitized subjects (14.2 p.p.b. vs. 10.1 p.p.b.; mean ratio 1.4, 95% CI: 1.1,1.9, p=,0.008). No difference was found between eNO levels in asthmatic subjects and control subjects exposed or unexposed to tobacco smoke. In conclusion, eNO concentrations are high in atopic asthmatic children and particularly high in atopic asthmatics who are sensitized to house-dust mite allergen. [source]

    Gene flow and melanism in garter snakes revisited: a comparison of molecular markers and island vs. coalescent models

    BIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 3 2003
    TONYA D. BITTNER
    Within populations, the stochastic effect of genetic drift and deterministic effect of natural selection are potentially weakened or altered by gene flow among populations. The influence of gene flow on Lake Erie populations of the common garter snake has been of particular interest because of a discontinuous colour pattern polymorphism (striped vs. melanistic) that is a target of natural selection. We reassessed the relative contributions of gene flow and genetic drift using genetic data and population size estimates. We compared all combinations of two marker systems and two analytical approaches to the estimation of gene flow rates: allozymes (data previously published), microsatellite DNA (new data), the island model (FST -based approach), and a coalescence-based approach. For the coalescence approach, mutation rates and sampling effects were also investigated. While the two markers produced similar results, gene flow based on FST was considerably higher (Nm > 4) than that from the coalescence-based method (Nm < 1). Estimates of gene flow are likely to be inflated by lack of migration-drift equilibrium and changing population size. Potentially low rates of gene flow (Nm < 1), small population size at some sites, and positive correlations of number of microsatellite DNA alleles and island size and between M, mean ratio of number of alleles to range in allele size, and island size suggest that in addition to selection, random genetic drift may influence colour pattern frequencies. © 2003 The Linnean Society of London, Biological Journal of the Linnean Society, 2003, 79, 389,399. [source]

    Pharmacokinetic Interaction of the Direct Renin Inhibitor Aliskiren with Furosemide and Extended-Release Isosorbide-5-Mononitrate in Healthy Subjects

    CARDIOVASCULAR THERAPEUTICS, Issue 4 2008
    Sujata Vaidyanathan
    This study investigated the pharmacokinetics, safety, and tolerability of aliskiren administered alone or in combination with either the loop diuretic furosemide or an oral extended-release formulation of isosorbide-5-mononitrate (ISMN). In separate studies, 22 healthy subjects (ages 18,45 years) received either ISMN 40 mg or furosemide 20 mg once-daily for 3 days followed by a 3-day washout. Subjects then received aliskiren 300 mg once-daily for 7 days followed by combination therapy for 3 days. Pharmacokinetic assessments were taken at regular intervals over 24 h after dosing on the last day of each treatment period. At steady state, aliskiren AUC, was decreased by 7% (geometric mean ratio [90% CI], 0.93 [0.84, 1.04]), and Cmax by 20% (0.80 [0.65, 0.97]) with furosemide coadministration compared with aliskiren administration alone. Aliskiren coadministration reduced furosemide AUC, by 28% (0.72 [0.64, 0.81]) and Cmax by 49% (0.51 [0.39, 0.66]) compared with furosemide alone. Coadministration of aliskiren and ISMN was associated with only minor changes in the pharmacokinetic parameters of aliskiren (AUC, 1.03 [0.90, 1.18]; Cmax 0.94 [0.69, 1.29]) and ISMN (AUC, 0.88 [0.71, 1.10]; Cmax 0.94 [0.79, 1.13]). Headache and dizziness were the most common adverse events in both studies; dizziness and BP values below normal (SBP <90 and/or DBP <50 mmHg) were more frequent with aliskiren and ISMN coadministration than with either agent alone. Coadministration of aliskiren and ISMN had no clinically relevant effect on either aliskiren or ISMN pharmacokinetics. In conclusion, coadministration of aliskiren and furosemide reduced furosemide exposure and had a minor effect on aliskiren pharmacokinetics. The clinical significance of reduced systemic exposure to furosemide during coadministration of aliskiren is uncertain. [source]

    Is the effect of probiotics on atopic dermatitis confined to food sensitized children?

    CLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2006
    D. Sistek
    Summary Background Probiotics have previously been shown to reduce the severity of atopic dermatitis (AD) in infants and children. Objective To examine the effect of two probiotics (Lactobacillus rhamnosus and Bifidobacteria lactis) on established AD in children. Subjects and methods Atopic children with current dermatitis received 2 × 1010 colony forming units/g of probiotic (n=29) or placebo (n=30). Both were given daily as a powder mixed with food or water. SCORing Atopic Dermatitis (SCORAD; developed by the European Task Force on Atopic Dermatitis) a measure of the extent and severity of AD, was assessed at baseline, 2 and 12 weeks after starting treatment and 4 weeks after treatment was discontinued. Results SCORAD geometric mean score at baseline was 26.0 (21.9,30.8) in the probiotic group and 35.1 (28.9,42.8) in the placebo group (P=0.02). After adjustment for these between-group baseline differences there was no significant improvement in AD at 12 weeks, SCORAD geometric mean ratio: 0.80 (95% confidence level (CI) 0.62,1.04, P=0.10). Among the food sensitized children, there was an improvement in those treated with probiotics, SCORAD geometric mean ratio: 0.73 (95% CI 0.54,1.00, P=0.047). Conclusion In this study a combination of Lactobacillus rhamnosus and Bifidobacteria lactis improved AD only in food sensitized children. [source]

    Bovine-HA spongiosa blocks and immediate implant placement in sinus augmentation procedures

    CLINICAL ORAL IMPLANTS RESEARCH, Issue 4 2002
    Histopathological, histomorphometric observations on different histological stainings in 10 consecutive patients
    Abstract: Bovine mineral spongiosa block (B-SB) was used as a bone substitute in sinus augmentation procedures in 10 consecutive patients. Implants were placed during the same session. The purpose of this study was to histopathologically examine the healing of the grafted site around the implants at 12 months. Radiographic follow-up showed apparent bone apposition in the augmented area around the implants. Clinically, all 36 implants were stable and integrated with the surrounding tissue. Histopathologically, new bone formation was evident in all specimen hard tissue cores. Hydroxyapatite particles were present in direct contact with the remodeled osseous tissue. Mallory trichrome staining showed different stages of mineralization and maturation of the newly formed bone around the grafted mineral particles. Morphometric evaluation of Picrosirius red stained slides under polarized light microscopy was performed at the peripheral/external and deep section slides of all specimens. The average bone area fraction was 34.2%, with a 1 : 5.4 mean lamellar/woven bone ratio at the peripheral side and 53.0%, with 1 : 2.5 mean ratio at the deep side. The differences of both parameters between the two sites were statistically significant. B-SB proved to be a suitable grafting material with simultaneously placed implants in sinus floor augmentation procedures. [source]

    Pharmacokinetics of carisbamate (RWJ-333369) in healthy Japanese and Western subjects

    EPILEPSIA, Issue 8 2009
    Peter Zannikos
    Summary Purpose:, To compare the pharmacokinetics of carisbamate (RWJ-333369) in healthy Japanese and Western adults, and to comparatively assess carisbamate safety and tolerability between the two populations. Methods:, An open-label study was conducted in 24 Japanese and 24 Caucasian healthy subjects. Subjects received a single oral dose of 250 mg carisbamate on day 1 followed by a 3-day washout period; twice-daily dosing of 250 mg carisbamate on days 5,8; subsequently, 500 mg on days 9,12 and a single dose of 500 mg on day 13. Plasma samples were collected for a pharmacokinetic analysis on days 1, 8, and 13. Plasma and urine samples were analyzed for carisbamate and its urinary metabolites by liquid-chromatography-mass-spectrometry. Results:, Following a single dose, carisbamate Cmax and area under the curve (AUC) geometric mean ratios were 16.4% and 28.8% higher in Japanese than in Caucasians, respectively; these differences were statistically significant and their 90% confidence intervals (CIs) fell outside of the 80,125% limits, which are considered not to be of clinical significance. With dose,body weight normalization, Cmax and AUC were similar in Japanese and Caucasian subjects and the 90% CIs were within the 80,125% boundaries. Carisbamate was well tolerated, and its mean oral clearance and half-life were similar in both groups, ranging from 35.1,41.4 ml/h/kg and 11.5,12.8 h. Discussion:, Carisbamate plasma exposure (AUC) and Cmax in Japanese subjects is ,20,25% higher than in Caucasians due to a higher mg/kg dose. After body weight normalization, carisbamate pharmacokinetics was similar between Japanese and Caucasian subjects following single and multiple dosing, and showed the same dose proportionality. [source]

    Evaluation of a new venom-based clotting assay of protein C

    INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2008
    P. C. COOPER
    Summary Congenital protein C deficiency significantly increases the risk of venous thromboembolism, a serious and potentially lethal condition. Protein C levels can be determined by chromogenic, clotting and antigenic assays, each type of assay has differences in specificity and sensitivity to protein C deficiency. In principle, clotting-based assays of protein C are preferred over chromogenic assays, as they can detect some rare mutations that are missed by the chromogenic assay, however, clotting-based assays may be prone to inaccuracy because of poor specificity. We have evaluated a new venom-based clotting assay of protein C, and optimized it for use on Sysmex CA-1500 analyser. The assay was linear from 0 to 130 U/dl, a normal plasma demonstrated good inter-assay precision, with a coefficient of variation of 4.8%. The assay compared well with antigenic- and venom-based chromogenic protein C assay in normal individuals, subjects with lupus anticoagulant, and subjects with FV Leiden. Median protein C levels by clotting, chromogenic and antigen for the three subject groups were 108 U/dl, 108 IU/dl and 109 IU/dl for normal subjects, 94 U/dl, 106 IU/dl and 103 IU/dl for subjects with lupus anticoagulant, and 102 U/dl, 104 IU/dl and 100 IU/dl for subjects heterozygous for FV Leiden. Comparing levels of clotting protein C with protein C antigen by ratio (clotting/antigen), the three groups showed small differences that did not quite reach statistical significance, (mean ratios ranged from 0.95 to 1.01, anovaP = 0.0561), the lowest ratio was with the lupus anticoagulant group. Comparing clotting assay with chromogenic assay by ratio (clotting/chromogenic), the three groups did show a statistically significant difference (P = 0.0033) which was due to a difference in mean ratios between normal and lupus anticoagulant groups (ratios 1.00 and 0.91, respectively, P < 0.01). There was no statistical difference in any of the groups when comparing chromogenic protein C with protein C antigen (mean ratios ranged from 1.02 to 1.05, P = 0.3925). In a normal sample, the clotting-based protein C level was unaffected by increasing FVIII level by up to 1000 IU/dl, using intermediate purity FVIII concentrate. The new assay is considered to be a suitable assay for the routine diagnosis of protein C deficiency. [source]

    INTERCOLONIAL VARIABILITY IN MACROMOLECULAR COMPOSITION IN P-STARVED AND P-REPLETE SCENEDESMUS POPULATIONS REVEALED BY INFRARED MICROSPECTROSCOPY,

    JOURNAL OF PHYCOLOGY, Issue 5 2008
    Philip Heraud
    Macromolecular variability in microalgal populations subject to different nutrient environments was investigated, using the chlorophyte alga Scenedesmus quadricauda (Turpin) Bréb. as a model organism. The large size of the four-cell coenobia in the strain used in this study (,35 ,m diameter) conveniently allowed high quality spectra to be obtained from individual coenobia using a laboratory-based Fourier transform infrared (FTIR) microscope with a conventional globar source of IR. By drawing sizable subpopulations of coenobia from two Scenedesmus cultures grown under either nutrient-replete or P-starved conditions, the population variability in macromolecular composition, and the effects of nutrient change upon this, could be estimated. On average, P-starved coenobia had higher carbohydrate and lower protein absorbance compared with P-replete coenobia. These parameters varied between coenobia with histograms of the ratio of absorbance of the largest protein and carbohydrate bands being Gaussian distributed. Distributions for the P-replete and P-starved subpopulations were nonoverlapping, with the difference in mean ratios for the two populations being statistically significant. Greater variance was observed in the P-starved subpopulation. In addition, multivariate models were developed using the spectral data, which could accurately predict the nutrient status of an independent individual coenobium, based on its FTIR spectrum. Partial least squares discriminant analysis (PLS-DA) was a better prediction method compared with soft independent modeling by class analogy (SIMCA). [source]

    A two-step coagulation test to identify anti,2 -glycoprotein I lupus anticoagulants

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2004
    V. Pengo
    Summary., Lupus anticoagulants (LA) are immunoglobulins which inhibit phospholipid (PL)-dependent coagulation tests. LA are not specific, as they may reflect the presence of antibodies to human prothrombin, human ,2 -Glycoprotein I (,2GPI), an association of previous antibodies or other antibodies. Antibodies to human ,2GPI act as in vitro anticoagulants by enhancing the binding of ,2GPI to PL, and this binding may be influenced by calcium ion concentration. A reduction in final calcium concentration, from 10 mm to 5 mm, increased coagulation times in both dilute Russell Viper Venom Time (dRVVT) and dilute Prothrombin Time (dPT) when plasmas of patients with anti,2GPI antibodies were used. Ten LA patients showed increased dRVVT and dPT ratios from means of 1.5 to 1.7 (P < 0.001) and 2.4 to 4.3 (P = 0.002), respectively. Instead, all LA-positive anti,2GPI antibody-negative patients showed decreased coagulation times from mean ratios of 1.5 to 1.3 (P = 0.004) in dRVVT and from 2.0 to 1.5 (P = 0.01) in dPT. These results are confirmed by running dRVVT of normal plasma spiked with affinity purified IgG anti,2GPI antibodies. Therefore, when a PL,dependent coagulation test is run twice, at different final calcium concentrations, anti,2GPI LA can be identified. [source]

    The effects of ritonavir and lopinavir/ritonavir on the pharmacokinetics of a novel CCR5 antagonist, aplaviroc, in healthy subjects

    BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2006
    Kimberly 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]

    Pharmacokinetic interaction study between eslicarbazepine acetate and lamotrigine in healthy subjects

    ACTA NEUROLOGICA SCANDINAVICA, Issue 4 2010
    L. Almeida
    Almeida L, Nunes T, Sicard E, Rocha J-F, Falcăo A, Brunet J-S, Lefebvre M, Soares-da-Silva P. Pharmacokinetic interaction study between eslicarbazepine acetate and lamotrigine in healthy subjects. Acta Neurol Scand: 2010: 121: 257,264. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, Anti-epileptic drugs are often used in combination. Both eslicarbazepine (main metabolite of eslicarbazepine acetate, ESL) and lamotrigine undergo conjugation with glucuronic acid, and both eslicarbazepine and its glucuronide and lamotrigine glucuronide undergo extensive renal elimination; therefore, there is a potential for interaction. This study investigated the interaction between ESL and lamotrigine in healthy subjects. Methods,,, Open-label study in two parallel groups of 16 healthy volunteers each. After an 8-day treatment with ESL or lamotrigine, ESL (1200 mg once-daily) and lamotrigine (150 mg once-daily) were co-administered for 19 days. Geometric mean ratios (GMR) and 90% confidence intervals (90% CI) for maximum plasma concentration (Cmax) and area under the plasma concentration,time curve in the dosing interval (AUC0,24) were calculated for eslicarbazepine (ESL active metabolite) and lamotrigine. Results,,, The Cmax and AUC0,24 GMR (90% CI) were, respectively, 95% (87,102%) and 96% (91,102%) for eslicarbazepine, and 88% (82,94%) and 86% (81,92%) for lamotrigine. The 90% CI of the Cmax and AUC0,24 GMR fell within the prespecified acceptance interval (80,125%) both for eslicarbazepine and lamotrigine. Conclusion,,, There was no significant pharmacokinetic interaction between ESL and lamotrigine in healthy subjects. Therefore, no dosage adjustment appears to be usually required in either lamotrigine or ESL when the drugs are co-administered. [source]

    Crushed Clopidogrel Administered via Nasogastric Tube Has Faster and Greater Absorption than Oral Whole Tablets

    JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 4 2009
    M. UROOJ ZAFAR M.B.B.S.
    Objectives: To compare the absorption of 300 mg clopidogrel administered crushed via nasogastric (NG) tube versus whole tablets taken orally in healthy volunteers. Background: Earlier antiplatelet therapy has proven benefits in treatment of myocardial infarction and in patients undergoing PCI. Aspirin can be delivered early in crushed form via NG tube after CABG surgery to prevent graft occlusion. If clopidogrel given crushed via NG tube provides faster absorption, it could allow earlier clopidogrel loading. Methods: Nine healthy human subjects (34.7 ± 11.1 years, 5 males) were given 300 mg clopidogrel in crushed form via NG tube with 30 mL water after 8 hours of fasting. Plasma levels of the primary circulating inactive clopidogrel metabolite SR26334 were measured after 20 minutes, 40 minutes, 1, 2, 4, 8, 12, and 24 hours of dosing. Following ,2 week washout, same subjects swallowed 300 mg clopidogrel (four 75 mg tablets) after an 8-hour fasting and SR26334 levels were measured at the same time points. Results: Plasma SR26334 concentrations peaked earlier after crushed delivery than after oral intake (44 vs. 70 minutes, P = 0.023) and the median peak was 80% higher (13,083 vs. 7,255 ng/mL, respectively, P = 0.021). At 40 minutes, area under the curve was almost twofold greater with NG administration than oral administration (geometric means ratio = 0.5299, 95% CI = 0.28,0.99, P = 0.048), but was similar over the 24-hour period with both administration methods (geometric means ratio = 1.05, 95% CI = 0.84,1.32, P = 0.646). Conclusions: A 300 mg loading dose of crushed clopidogrel administered via NG tube provides faster and greater bioavailability than an equal dose taken orally as whole tablets. The clinical benefits of this strategy need to be investigated. [source]

    Strategies to improve efficacy and safety of a novel class of antiviral hyper-activation-limiting therapeutic agents: the VS411 model HIV/AIDS

    BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2010
    D De Forni
    BACKGROUND AND PURPOSE Antiviral hyper-activation-limiting therapeutic agents (AV-HALTs) are a novel experimental drug class designed to both decrease viral replication and down-regulate excessive immune system activation for the treatment of chronic infections, including human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. VS411, a first-in-class AV-HALT, is a single-dosage form combining didanosine (ddI, 400 mg), an antiviral (AV), and hydroxyurea (HU, 600 mg), a cytostatic agent, designed to provide a slow release of ddI to reduce its maximal plasma concentration (Cmax) to potentially reduce toxicity while maintaining total daily exposure (AUC) and the AV activity. EXPERIMENTAL APPROACH This was a pilot phase I, open-label, randomized, single-dose, four-way crossover trial to investigate the fasted and non-fasted residual variance of AUC, Cmax and the oral bioavailability of ddI and HU, co-formulated as VS411, and administered as two different fixed-dose combination formulations compared to commercially available ddI (Videx EC) and HU (Hydrea) when given simultaneously. KEY RESULTS Formulation VS411-2 had a favourable safety profile, displayed a clear trend for lower ddI Cmax (P= 0.0603) compared to Videx EC, and the 90% confidence intervals around the least square means ratio of Cmax did not include 100%. ddI AUC, was not significantly decreased compared to Videx EC. HU pharmacokinetic parameters were essentially identical to Hydrea, although there was a decrease in HU exposure under fed versus fasted conditions. CONCLUSIONS AND IMPLICATIONS A phase IIa trial utilizing VS411-2 formulation has been fielded to identify the optimal doses of HU plus ddI as an AV-HALT for the treatment of HIV disease. [source]