Generic substitution: the use of medicinal products containing different salts and implications for safety and efficacy

In their quest to gain early entry of new generic products into the market prior to patent expiration, one of the strategies pursued by generic drug product manufacturers is to incorporate different salts of an approved active pharmaceutical ingredient (API) in a brand company's marketed dosage form and subject such dosage forms to bioequivalence assessment. These initiatives present challenges to regulatory authorities where the decision to approve bioequivalent products containing such pharmaceutical alternatives must be considered in the light of safety and efficacy, and more particularly, with respect to their substitutability. This article describes the various issues and contentions associated with the concept of pharmaceutical alternatives, specifically with respect to the uses of different salts and the implications for safety, efficacy and generic substitution

Phenylpropanolamine hydrochloride

Phenylpropanolamine hydrochloride belongs to the sympathomimetic amine class of drugs and is structurally related to ephedrine hydrochloride. Its synthesis was first reported in 1910 and the first American patent was registered in 1939. The effects of phenylpropanolamine hydrochloride are largely the result of alpha-adrenergic agonist activity resulting from both direct stimulation of adrenergic receptors and release of neuronal norepinephrine. The principal adverse effect of phenylpropanolamine hydrochloride is dose-related hypertension and ventricular arrhythmia has been described. Phenylpropanolamine hydrochloride is widely used as a decongestant and it has been used as an anorectic agent for over 40 years. A report in 1939 described its effect as an hypertensive agent when administered parenterally

Pharmacokinetics of phenylpropanolamine in humans after a single dose study

The pharmacokinetics of phenylpropanolamine have been studied in healthy human volunteers following the oral administration of an aqueous solution of the drug (50 mg/200 ml). Blood and urine samples collected throughout the trial were assayed using HPLC with UV detection. The drug was shown to be rapidly absorbed with a mean tmax of 1.47 ± 0.49 h and a mean elimination half-life of 4.0 ± 0.5 h. Phenylpropanolamine is predominantly excreted via the kidney with a mean renal clearance of 0.646 ± 0.089 liter/kg/h and 90.2 ± 1.7% excreted unchanged in the urine. The data were not well described using conventional one or two body compartment models. However, the incorporation of a discontinuous absorption phase into the models resulted in an improved overall fit with better characterisation of the absorption phase

In vitro-in vivo evaluation of a sustained release phenylpropanolamine oral dosage form

There is increasing interest in measuring pharmacokinetic parameters of phenylpropanolamine (PPA), a sympathomimetic amine used in over-the-counter nasal decongestants and anorectic formulations. A high pressure liquid chromatographic (HPLC) procedure was developed to enable direct ultraviolet detection of PPA, after extraction from serum and urine, without prior derivatization of the drug. This method was used to assay samples obtained from a bioavailability study of BUBtained-releasePPA tablets. The mean serum and urine profiles obtained are presented. The sustained-release tablets were subjected to dissolution testing utilizing the United States Pharmacopoeia (USP XIX) rotating basket method. An internal standard was incorporated into the dissolution fluid to enable direct analysis of the samples by HPLC. A comparison of three different dissolution fluid regimens was carried out to determine if release of the drug was affected by the change in pH of the medium and to select the most convenient method for the final dissolution studies. Some preliminary observations relating to correlations between rate of drug release from the sustained-release dosage form and percent drug absorbed are presented

Determination of phenylpropanolamine in serum and urine by high performance liquid chromatography

A high-performance liquid chromatographic analysis of phenylpropanolamine in human serum and urine without prior derivatization is presented. Using direct UV detection the method is sufficiently sensitive to detect 25 ng of drug/ml of serum or urine; the coefficients of variation at 25 ng/ml and 500 ng/ml were 5.16 and 2.12, respectively, in serum. The method involves serum and urine extraction at a basic pH with chloroform, a single back-extraction, and chromatography on a reverse-phase column. Serum and urine data following administration of a single 150-mg sustained-release tablet of phenylpropanolamine hydrochloride in 6 healthy volunteers demonstrates the suitability of the analytical method

The effect of selection on genetic parameter estimates

A simulation study was carried out to investigate the effect of selection on the estimation of genetic parameters for butterfat production in dairy cattle. It was found that selection leads to a substantial overestimation of fixed effects and variance components and an underestimation of heritability estimates. This effect was attributed to the fact that all information on all animals in the analysis should be available to compensate for the effect of selection. (South African Journal of Animal Science, 2001, 31(2): 107-114

A comparison between single and composite milk samples for the genetic evaluation of milk composition in dairy cattle

A simulation study was carried out to compare the use of single and composite milk samples for the evaluation of milk composition in dairy cattle. The genetic correlation between the two sampling methods was estimated. Results showed a high genetic correlation between the breeding values arrived from composite and single samples. This indicates that the same genes are possibly responsible for both traits, which makes it possible to use a single sample, instead of a composite sample, in predicting breeding values. South African Journal of Animal Science Vol.32(1) 2002: 44-4

Future time perspective:A systematic review and meta-analysis

The ability to foresee, anticipate, and plan for future desired outcomes is crucial for wellbeing, motivation, and behavior. However, theories in organizational psychology do not incorporate time-related constructs such as Future Time Perspective (FTP), and research on FTP remains disjointed and scattered, with different domains focusing on different aspects of the construct, using different measures, and assessing different antecedents and consequences. In this review and meta-analysis, we aim to clarify the FTP construct, advance its theoretical development, and demonstrate its importance by: (a) integrating theory and empirical findings across different domains of research in order to identify major outcomes and antecedents of FTP, and (b) empirically examining whether and how these variables are moderated by FTP measures and dimensions. Results of a meta-analysis of k = 212 studies reveal significant relationships between FTP and major classes of consequences (i.e., those related to achievement, well-being, health behavior, risk behavior, and retirement planning), and between antecedents and FTP, as well as moderating effects of different FTP measures and dimensions. Highlighting the importance of FTP for organizational psychology theories, our findings demonstrate that FTP predicts these outcomes over-and-above the big five personality traits and mediates the associations between these personality traits and outcomes

Future time perspective and promotion focus as determinants of intraindividual change in work motivation

In the near future, workforces will increasingly consist of older workers. At the same time, research has demonstrated that work-related growth motives decrease with age. Although this finding is consistent with life span theories, such as the selection optimization and compensation (SOC) model, we know relatively little about the process variables that bring about this change in work motivation. Therefore, we use a 4-wave study design to examine the mediating role of future time perspective and promotion focus in the negative association between age and work-related growth motives. Consistent with the SOC model, we found that future time perspective was negatively associated with age, which, in turn, was associated with lower promotion focus, lower work-related growth motive strength, and lower motivation to continue working. These findings have important theoretical implications for the literature on aging and work motivation, and practical implications for how to motivate older workers

Development and exploratory cluster-randomised opportunistic trial of a theory-based intervention to enhance physical activity among adolescents

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