Home About us Contact
|
Home About us Contact | ||
|
|
||
Treatment Ratios (treatment + ratio)
Selected AbstractsHPA axis safety of fluticasone furoate nasal spray once daily in children with perennial allergic rhinitisPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2009Ita Tripathy The effects of intranasal corticosteroids (INSs) on the hypothalamic,pituitary,adrenal (HPA) axis should be assessed for any to be marketed INS. The objective of this study was to assess the effects of fluticasone furoate nasal spray (FFNS) on cortisol production (as a measure of HPA axis function) following 6 wk of treatment with FFNS 110 ,g once daily (QD) compared with placebo in pediatric patients with perennial allergic rhinitis (PAR). In this double-blind, parallel-group study, patients (n = 112) aged 2,11 yr with a 1-yr history of PAR (6 months for patients aged 2,3 yr) were randomized in a 1:1 ratio to either placebo or FFNS. Serum cortisol (SC) concentrations and urinary cortisol (UC) excretion were measured over a 24-h period at the randomization (baseline) and final treatment (week 6) visits for HPA axis evaluation in a domiciled environment (overnight in the clinic). Plasma samples were collected for FFNS at several time points over the 24 h after the final dose for pharmacokinetic analyses. FFNS was non-inferior to placebo with respect to change from baseline (expressed as a ratio) in 24-h SC weighted mean. The lower limit of the two-sided 95% confidence interval (CI) for the treatment ratio was greater than the pre-specified non-inferiority margin of 0.8 (treatment ratio = 0.97, 95% CI 0.88,1.07). UC excretion over 24 h at baseline and end of treatment was similar between treatment groups; no patients had 24-h excretion levels below normal range after 6 wk of treatment. Plasma concentrations of FFNS were generally non-quantifiable (<10 pg/ml). Results of the current study indicate that FFNS 110 ,g QD has no significant effect on HPA axis function in 2- to 11-yr-old pediatric patients with PAR. [source] Pharmacokinetic comparison of orally-disintegrating metoclopramide with conventional metoclopramide tablet formulation in healthy volunteersALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009R. FASS Summary Background, Oral tablet formulations of metoclopramide are effective therapies for gastroparesis and gastro-oesophageal reflux disease; however, difficulty swallowing tablets or nausea/vomiting may reduce patient adherence to therapy. Because of this, a metoclopramide orally-disintegrating tablet (ODT) has been developed. Aim, To evaluate the bioequivalence of a single administration of a 10-mg metoclopramide ODT and a conventional 10-mg oral metoclopramide tablet in healthy volunteers. Methods, In a randomized, single-dose, crossover study, healthy volunteers received single administration of 10-mg metoclopramide ODT and 10-mg conventional metoclopramide tablet, with a 7-day interval between treatments. Serial blood samples were collected before dosing and during 24 h post-treatment. Results, Forty-one volunteers completed both treatment arms. Metoclopramide ODT was bioequivalent to conventional tablets; 90% CIs for geometric mean treatment ratios of Cmax [91.6% (90% CI, 87.7,95.8%)], AUClast [97.3% (90% CI, 94.5,100.2%)] and AUCinf [97.6% (90% CI, 94.5,100.8%)] were within the predefined range. Of the 44 volunteers included in the safety analysis, 9 (20%) reported AEs after ODT, compared with 13 (30%) after conventional tablets. Conclusion, In healthy volunteers, single administration of 10-mg metoclopramide ODT was well tolerated and bioequivalent to single administration of a conventional 10-mg metoclopramide tablet. [source] Industrial sectors with high risk of women's hospital-treated injuriesAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 1 2007Pete Kines PhD Abstract Background Women's occupational injury rates are converging with those of males. Associations between female workers' hospital treated injury rates, industrial sector and injured body area were analyzed to provide for better-focused injury prevention of women's hazardous jobs. Methods Females' standardized hospital treatment ratios (SHR) and the excess fraction for five body regions (head/neck, thorax, back, upper and lower extremities) were calculated for 58 industrial sectors for 1999,2003. Results Five industrial sectors, "Cleaning, laundries and dry cleaners," "Transport of passengers," "Hotels and restaurants," "Hospitals" and "Transport of goods" had significantly high SHRs for all five body regions. The excess fraction for upper extremity injuries revealed that 14%,27% of injuries could theoretically have been avoided. Conclusions There is strong evidence for an association between women's hospital treated injuries and industrial sector. The results justify the need for gender-sensitive analyses to orient injury prevention programs. Am. J. Ind. Med. 50:13,21, 2007. © 2006 Wiley-Liss, Inc. [source] Pharmacokinetic assessment of a five-probe cocktail for CYPs 1A2, 2C9, 2C19, 2D6 and 3ABRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2009Sandrine Turpault WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Numerous cocktails using concurrent administration of several cytochrome P450 (CYP) isoform-selective probe drugs have been reported to investigate drug,drug interactions in vivo. , This approach has several advantages: characterize the inhibitory or induction potential of compounds in development toward the CYP enzymes identified in vitro in an in vivo situation, assess several enzymes in the same trial, and have complete in vivo information about potential CYP-based drug interactions. WHAT THIS STUDY ADDS , This study describes a new cocktail containing five probe drugs that has never been published. , This cocktail can be used to test the effects of a new chemical entity on multiple CYP isoforms in a single clinical study: CYP1A2 (caffeine), CYP2C9 (warfarin), CYP2C19 (omeprazole), CYP2D6 (metoprolol), and CYP3A (midazolam) and was designed to overcome potential liabilities of other reported cocktails. AIMS To assess the pharmacokinetics (PK) of selective substrates of CYP1A2 (caffeine), CYP2C9 (S-warfarin), CYP2C19 (omeprazole), CYP2D6 (metoprolol) and CYP3A (midazolam) when administered orally and concurrently as a cocktail relative to the drugs administered alone. METHODS This was an open-label, single-dose, randomized, six-treatment six-period six-sequence William's design study with a wash-out of 7 or 14 days. Thirty healthy male subjects received 100 mg caffeine, 100 mg metoprolol, 0.03 mg kg,1 midazolam, 20 mg omeprazole and 10 mg warfarin individually and in combination (cocktail). Poor metabolizers of CYP2C9, 2C19 and 2D6 were excluded. Plasma samples were obtained up to 48 h for caffeine, metoprolol and omeprazole, 12 h for midazolam, 312 h for warfarin and the cocktail. Three different validated liquid chromatography tandem mass spectrometry methods were used. Noncompartmental PK parameters were calculated. Log-transformed Cmax, AUClast and AUC for each analyte were analysed with a linear mixed effects model with fixed term for treatment, sequence and period, and random term for subject within sequence. Point estimates (90% CI) for treatment ratios (individual/cocktail) were computed for each analyte Cmax, AUClast and AUC. RESULTS There was no PK interaction between the probe drugs when administered in combination as a cocktail, relative to the probes administered alone, as the 90% CI of the PK parameters was within the prespecified bioequivalence limits of 0.80, 1.25. CONCLUSION The lack of interaction between probes indicates that this cocktail could be used to evaluate the potential for multiple drug,drug interactions in vivo. [source] | ||||||||||