Pharmacokinetic behaviour of the chemoprotectants BNP7787 and mesna after an i.v. bolus injection in rats

0.01). In conclusion, the five-fold higher AUC of mesna in plasma after mesna administration and the fact that mesna is more reactive with (hydrated) cisplatin than its disulphide form BNP7787 represent a plausible explanation as to why mesna administration can reduce the antitumour activity of cisplatin. After BNP7787 administration, the distribution of BNP7787 and mesna was restricted to the kidney, which confirmed the selective protection of the kidney by BNP7787

Personality psychology: Lexical approaches, assessment methods, and trait concepts reveal only half of the story—Why it is time for a paradigm shift

This article develops a comprehensive philosophy-of-science for personality psychology that goes far beyond the scope of the lexical approaches, assessment methods, and trait concepts that currently prevail. One of the field’s most important guiding scientific assumptions, the lexical hypothesis, is analysed from meta-theoretical viewpoints to reveal that it explicitly describes two sets of phenomena that must be clearly differentiated: 1) lexical repertoires and the representations that they encode and 2) the kinds of phenomena that are represented. Thus far, personality psychologists largely explored only the former, but have seriously neglected studying the latter. Meta-theoretical analyses of these different kinds of phenomena and their distinct natures, commonalities, differences, and interrelations reveal that personality psychology’s focus on lexical approaches, assessment methods, and trait concepts entails a) erroneous meta-theoretical assumptions about what the phenomena being studied actually are, and thus how they can be analysed and interpreted, b) that contemporary personality psychology is largely based on everyday psychological knowledge, and c) a fundamental circularity in the scientific explanations used in trait psychology. These findings seriously challenge the widespread assumptions about the causal and universal status of the phenomena described by prominent personality models. The current state of knowledge about the lexical hypothesis is reviewed, and implications for personality psychology are discussed. Ten desiderata for future research are outlined to overcome the current paradigmatic fixations that are substantially hampering intellectual innovation and progress in the field

The chemical reactivity of BNP7787 and its metabolite mesna with the cytostatic agent cisplatin: comparison with the nucleophiles thiosulfate, DDTC, glutathione and its disulfide GSSG.

PURPOSE: BNP7787 is a new chemoprotective agent presently under clinical investigation to protect against cisplatin-induced toxicities, especially nephrotoxicity and neurotoxicity. In the kidneys BNP7787 is postulated to undergo selective conversion into mesna, which can locally detoxify cisplatin. The reactivity of cisplatin with this new chemoprotective agent and with its metabolite mesna was investigated at clinically observed plasma concentrations and compared with the nucleophiles thiosulfate (TS) and DDTC, and with the endogenous compounds glutathione (GSH) and oxidized glutathione (GSSG). METHODS: Reaction kinetics experiments were performed at 37 degrees C and pH 7.4 in the presence of a high chloride concentration (0.15 M). The degradation of cisplatin was measured over time using HPLC with off-line flameless atomic absorption spectrophotometry. RESULTS: The degradation half-lives of cisplatin (13.5 microM) with 17.2 m M BNP7787, 340 microM mesna and 17.2 m M mesna were 124 min, about 790 min and 73 min, respectively. Cisplatin reacted at least 9.5 times more slowly with 17.2 mM BNP7787 and 5.5 times more slowly with 17.2 mM mesna than with 17.2 mM of the modulating agents DDTC or TS (i.e. half-lives 11 and 13 min, respectively). The half-lives of cisplatin with 17.2 m M GSH and GSSG (i.e. 122 and 115 min, respectively) were comparable with the half-life obtained with BNP7787. The thiol mesna was shown to be a stronger nucleophile than its corresponding disulfide BNP7787. CONCLUSIONS: The much slower relative reactivity of BNP7787, the short residence of BNP7787 (approximately 2 h) and the much lower concentration of mesna in the circulation following BNP7787 administration precludes chemical inactivation of cisplatin in the circulation, and thus the antitumor activity of cisplatin is maintained

Pharmacokinetics of BNP7787 and its metabolite mesna in plasma and ascites: a case report.

PURPOSE: BNP7787 (2',2'-dithio-bis-ethane sulfonate sodium) is a novel protector against cisplatin-induced toxicities. The pharmacokinetics of BNP7787 and its metabolite mesna were investigated in plasma and ascites of a cancer patient. We also evaluated potential pharmacokinetic interactions between BNP7787 and cisplatin. METHODS: BNP7787 and mesna were measured as mesna in deproteinized plasma and ascites using high-performance liquid chromatography with an electrochemical detector provided with a wall-jet gold electrode. RESULTS: After the i.v. administration of 41 g/m(2) BNP7787, BNP7787 and mesna had a half-life of 1.5 and 3.4 h, respectively. The AUC( infinity ) of mesna was approximately 8% of the AUC( infinity ) of BNP7787. Coadministration of cisplatin did not appear to influence the plasma concentration-time curves of BNP7787 and mesna. In ascites, approximately 0.02% of the BNP7787 dose was present as mesna, whereas approximately 4% of the dose was present as BNP7787 at the time of the maximum concentration. CONCLUSIONS: It can be concluded that the presence of ascites did not have a major impact on the pharmacokinetics of BNP7787 and coadministration of cisplatin did not influence the pharmacokinetics of BNP7787 and mesna