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Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence and absence of food.

ABSTRACT: The objective of this study was to compare the pharmacokinetic profile of a novel, once-daily, controlled-release formulation of hydromorphone (OROS hydromorphone) under fasting conditions with that immediately after a high-fat breakfast in healthy volunteers. The effect of the opioid antagonist naltrexone on fasting hydromorphone pharmacokinetics also was evaluated.In an open-label, three-way, crossover study, 30 healthy volunteers were randomized to receive a single dose of 16 mg OROS hydromorphone under fasting conditions, 16 mg OROS hydromorphone under fed conditions, or 16 mg OROS hydromorphone under fasting conditions with a naltrexone 50-mg block. Plasma samples taken pre-dose and at regular intervals up to 48 hours post-dose were assayed for hydromorphone concentrations. Analysis of variance was performed on log-transformed data; for mean ratios of 0.8 to 1.2 (20%), differences were considered minimal. Bioequivalence was reached if 90% confidence intervals (CI) of treatment mean ratios were between 80% and 125%.The mean geometric ratios of the fed and fasting treatment groups for maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-t; AUC0-infinity) were within 20%. Confidence intervals were within 80% to 125% for AUC0-t and AUC0-infinity but were slightly higher for Cmax (105.9% and 133.3%, respectively). With naltrexone block, the hydromorphone Cmax increased by 39% and the terminal half-life decreased by 4.5 hours. There was no significant change in Tmax, AUC0-t or AUC0-infinity.Standard bioavailability measures show minimal effect of food on the bioavailability of hydromorphone from OROS hydromorphone. Naltrexone co-administration results in a slight increase in the rate of absorption but not the extent of absorption.

SUBMITTER: Sathyan G

PROVIDER: S-EPMC1810515 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence and absence of food.

Sathyan Gayatri G Xu Emily E Thipphawong John J Gupta Suneel K SK

BMC clinical pharmacology 20070202

<h4>Background</h4>The objective of this study was to compare the pharmacokinetic profile of a novel, once-daily, controlled-release formulation of hydromorphone (OROS hydromorphone) under fasting conditions with that immediately after a high-fat breakfast in healthy volunteers. The effect of the opioid antagonist naltrexone on fasting hydromorphone pharmacokinetics also was evaluated.<h4>Methods</h4>In an open-label, three-way, crossover study, 30 healthy volunteers were randomized to receive a ...[more]

PMID: 17270055

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Project description:BackgroundMonitoring salt consumption in children is essential for informing and implementing public health interventions to reduce children's salt intake. However, collection of 24-hour urines, considered as the most reliable approach, can be especially challenging to school children. This study aimed to assess the agreement between 24-hour urine (24hrU) and 24-hour food recall (24hrFR) in: (1) estimating salt intake in children; (2) classifying salt intakes above the recommended upper level set for children, and; (3) estimating change in mean salt intake over time.MethodsThis study utilised data from two cross-sectional surveys of school children aged 8 to 12 years living in the state of Victoria, Australia. A single 24hrU and 24hrFR were collected from each participant. Suspected inaccurate urine collections and implausible energy intakes were excluded based on pre-defined criteria. The agreement between the two methods was assessed using Bland-Altman methodology, the intraclass correlation coefficient (ICC), and the kappa statistic. The difference between the measured change in salt intake over time using 24hrU and 24hrFR was derived using mixed effects linear regression analysis.ResultsA total of 588 participants provided a 24hrU and 24hrFR. Overall, there was no meaningful difference in mean estimated salt intake between the two methods (- 0.2 g/day, 95% CI - 0.5 to 0.1). The Bland-Altman plot showed wide 95% limits of agreement (- 7.2 to 6.8). The ICC between the two methods was 0.13 (95% CI 0.05 to 0.21). There was poor interrater reliability in terms of classifying salt intake above the recommended upper level for children, with an observed agreement of 63% and kappa statistic of 0.11. The change in mean salt intake over time was 0.2 g/day (- 0.4 to 0.7) based on 24hrU, and 0.5 g/day (- 0.0 to 1.1) based on 24hrFR, with a difference-in-differences of 0.4 g/day (- 0.3 to 1.1).Conclusions24hrFR appears to provide a reasonable estimate of mean salt intake as measured by 24hrU in Australian school children. However, similar to previous observations in adults, and of studies exploring other alternative methods for estimating salt intake, 24hrFR is a poor predictor of individual-level salt intake in children.

Project description:Vancomycin has been associated with acute kidney injury in preclinical and clinical settings; however, the precise exposure profiles associated with vancomycin-induced acute kidney injury have not been defined. We sought to determine pharmacokinetic/pharmacodynamics indices associated with the development of acute kidney injury using sensitive urinary biomarkers. Male Sprague-Dawley rats received clinical-grade vancomycin or normal saline as an intraperitoneal injection. Total daily doses between 0 and 400 mg/kg of body weight were administered as a single dose or 2 divided doses over a 24-h period. At least five rats were utilized for each dosing protocol. A maximum of 8 plasma samples per rat were obtained, and urine was collected over the 24-h period. Kidney injury molecule-1 (KIM-1), clusterin, osteopontin, cystatin C, and neutrophil gelatinase-associated lipocalin levels were determined using Milliplex multianalyte profiling rat kidney panels. Vancomycin plasma concentrations were determined via a validated high-performance liquid chromatography methodology. Pharmacokinetic analyses were conducted using the Pmetrics package for R. Bayesian maximal a posteriori concentrations were generated and utilized to calculate the 24-h area under the concentration-time curve (AUC), the maximum concentration (Cmax), and the minimum concentration. Spearman's rank correlation coefficient (rs ) was used to assess the correlations between exposure parameters, biomarkers, and histopathological damage. Forty-seven rats contributed pharmacokinetic and toxicodynamic data. KIM-1 was the only urinary biomarker that correlated with both composite histopathological damage (rs = 0.348, P = 0.017) and proximal tubule damage (rs = 0.342, P = 0.019). The vancomycin AUC and Cmax were most predictive of increases in KIM-1 levels (rs = 0.438 and P = 0.002 for AUC and rs = 0.451 and P = 0.002 for Cmax). Novel urinary biomarkers demonstrate that kidney injury can occur within 24 h of vancomycin exposure as a function of either AUC or Cmax.

Project description:Undernutrition remains highly prevalent in African children, highlighting the need for accurately assessing dietary intake. In order to do so, the assessment method must be validated in the target population. A triple pass 24 hour dietary recall with volumetric portion size estimation has been described but not previously validated in African children. This study aimed to establish the relative validity of 24-hour dietary recalls of daily food consumption in healthy African children living in Mbale and Soroti, eastern Uganda compared to simultaneous weighed food records. Quantitative assessment of daily food consumption by weighed food records followed by two independent assessments using triple pass 24-hour dietary recall on the following day. In conjunction with household measures and standard food sizes, volumes of liquid, dry rice, or play dough were used to aid portion size estimation. Inter-assessor agreement, and agreement with weighed food records was conducted primarily by Bland-Altman analysis and secondly by intraclass correlation coefficients and quartile cross-classification. 19 healthy children aged 6 months to 12 years were included in the study. Bland-Altman analysis showed 24-hour recall only marginally under-estimated energy (mean difference of 149kJ or 2.8%; limits of agreement -1618 to 1321kJ), protein (2.9g or 9.4%; -12.6 to 6.7g), and iron (0.43mg or 8.3%; -3.1 to 2.3mg). Quartile cross-classification was correct in 79% of cases for energy intake, and 89% for both protein and iron. The intraclass correlation coefficient between the separate dietary recalls for energy was 0.801 (95% CI, 0.429-0.933), indicating acceptable inter-observer agreement. Dietary assessment using 24-hour dietary recall with volumetric portion size estimation resulted in similar and acceptable estimates of dietary intake compared with weighed food records and thus is considered a valid method for daily dietary intake assessment of children in communities with similar diets. The method will be utilised in a sub-study of a large randomised controlled trial addressing treatment in severe childhood anaemia. This study was approved by the Mbale Research Ethics committee (Reference: 2013-050). Transfusion and Treatment of severe Anaemia in African Children: a randomized controlled Trial (TRACT) registration: ISRCTN84086586.

Project description:BackgroundStatistical methods to model the usual dietary intake of foods in a population generally ignore the additional information on the never-consumers. The objective of this study is to determine the added value of Food Frequency Questionnaire (FFQ) data allowing distinguishing the never-consumers from the non-consumers while modeling the usual intake distribution.MethodsThree food items with a different proportion of never-consumers were selected from the database of the Belgian food consumption survey of 2004 (N = 3200). The usual intake distribution for these food items was modeled with the Statistical Program for Analysis of Dietary Exposure (SPADE) and modeling parameters were extracted. These parameters were used to simulate (a) a new database with two 24-h recalls per respondent and (b) a "true" usual intake distribution. The usual intake distribution from the new database was obtained by modeling the 24-h recalls with SPADE, once without and once with the inclusion of the FFQ data on the never-consumers. Ratios were calculated for the different percentiles of the usual intake distribution: the modeled usual intake (g/day) (for both SPADE with and without the inclusion of FFQ data on never-consumers) was divided by the corresponding percentile of the simulated "true" usual intake (g/day). The closer the ratio is to one, the better the model fits the data.ResultsInclusion of the FFQ information to identify the never-consumers did not improve the estimation of the higher percentiles of the usual intake distribution. However, taking into account this FFQ information improved the estimation of the lower percentiles of the usual intake distribution even when the proportion of never-consumers was low.ConclusionsThe inclusion of FFQ information to identify the never-consumers is beneficial when interested in the whole usual intake distribution or in the lower percentiles only, no matter how low the proportion of never-consumers for that food item may be. However, when interest is only in the higher percentiles of the usual intake distribution, inclusion of FFQ information to identify the never-consumers will have no benefit.

Dataset Information

Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence and absence of food.

Publications

Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence and absence of food.

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