International journal of clinical pharmacology, therapy, and toxicology 

About: International journal of clinical pharmacology, therapy, and toxicology is an academic journal. The journal publishes majorly in the area(s): Pharmacokinetics & Bioavailability. It has an ISSN identifier of 0174-4879. Over the lifetime, 1632 publications have been published receiving 15782 citations.

Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation.

Abstract: A new model for evaluating nonsteroidal anti-inflammatory drugs (NSAIDs) is described. In this model of postoperative inflammation, the anti-inflammatory activity of curcumin (diferuloyl methane) was investigated in comparison with phenylbutazone and placebo. Phenylbutazone and curcumin produced a better anti-inflammatory response than placebo.

A distribution-free procedure for the statistical analysis of bioequivalence studies.

Abstract: In bioequivalence assessment, the consumer risk of erroneously accepting bioequivalence is of primary concern. In order to control the consumer risk, the decision problem is formulated with bioinequivalence as hypothesis and bioequivalence as alternative. In the parametric approach, a split into two one-sided test problems and application of two-sample t-tests have been suggested. Rejection of both hypotheses at nominal alpha-level is equivalent to the inclusion of the classical (shortest) (1-2 alpha) 100%-confidence interval in the bioequivalence range. This paper demonstrates that the rejection of the two one-sided hypotheses at nominal alpha-level by means of nonparametric Mann-Whitney-Wilcoxon tests is equivalent to the inclusion of the corresponding distribution-free (1-2 alpha) 100%-confidence interval in the bioequivalence range. This distribution-free (nonparametric) approach needs weaker model assumptions and hence presents an alternative to the parametric approach.

Sample size determination for bioequivalence assessment by means of confidence intervals

Abstract: The statistical analysis of bioequivalence assessment has been consolidated in recent years through the work of Schuirmann [1987], Westlake [1988] and Hauschke et al. [1990], and this has been reflected in the CPMP Note for Guidance on Bioavailability and Bioequivalence and in the joint recommendations of the APV (International Association for Pharmaceutical Technology) and ZL (Central Laboratories of German Pharmacists) during a recent workshop in support of EC-Guidelines [Blume et al. 1990]. Since the decision procedure based on the inclusion of the shortest 90%-confidence interval in the bioequivalence range is the procedure of choice, and as this is equivalent to the two one-sided tests procedure, the sample size determination is based on the power of the latter. Following the approach of Phillips [1990] for the additive model, corresponding nomograms for the more relevant multiplicative model are given in this paper for various ratios of the expected means for test and reference and various coefficients of variation.

Toxicodynamics of sulfur mustard.

Abstract: Mustards have become an important topic of global discussion in recent years. The latest extensive reports and conference of 145 nations in Paris (January 13, 1989) reveal that several countries have stockpiled large quantities of mustard gas. This situation creates an imminent danger to accidental or intentional exposure of this gas to civil populations throughout the world. In view of the sparse literature on the toxic nature of mustard gas, we have tried to present an integrated panorama of this compound and its derivatives. In this article, efforts were made to review mustard gas--its chemical nature, mode of action, methods available for its analysis in biological fluids and target organs, absorption, distribution, metabolism and excretion and its toxicity to various organs. The effects of mustard poisoning may be local, systemic, or both, depending on environmental conditions, exposed organs, and the extent and duration of exposure. The toxic effects of mustard include inhibition of mitosis, NAD depletion, decreased tissue respiration and finally cell death. Most of the toxic effects are related to alkylation of DNA. Mustards are also selective in their accumulation in fat tissue. The immediate organs affected after mustard exposure are skin, eyes, and lungs. Sulfur mustard has also been reported to be a potent carcinogen. Burns caused by mustard are severe and require long healing periods. Depending on the type and time of exposure, mustard renders persons disabled temporarily or permanently. Various antidotes such as sodium thiosulfate, dexamethasone, promethazine, heparin, vitamin E and atropine have been recommended for combating mustard poisoning. Protective clothing can substantially reduce the toxic effects of mustard exposure. The best possible way of eliminating mustard hazard is to ban its use completely.

Cmax/AUC is a clearer measure than Cmax for absorption rates in investigations of bioequivalence.

Abstract: In bioequivalence studies, the maximum concentration (Cmax) is shown to reflect not only the rate but also the extent of absorption. Cmax is highly correlated with the area under the curve (AUC) contrasting blood concentration with time. Therefore, use of the Cmax/AUC ratio is recommended for assessing the equivalence of absorption rates. The ratio is independent of both intrasubject variations and possible differences in the extent of absorption and reflects only the contrast between the absorption and disposition rate constants (ka/k).