ISSN:0142-2782    

DOI:10.1002/bdd.2510060302

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractLidocaine shows pronounced first‐pass metabolism upon peroral administration in man (about 30 per cent peroral bioavailability). Since the rectal bioavailability is about 65 per cent in man it is assumed that some drug is directly absorbed into systemic circulation by‐passing the liver. In rats peroral bioavailability is about 8 per cent whereas rectal bioavailability is about 100 per cent. This indicates that the rat is not a suitable model to study rectal lidocaine dosage forms. The purpose of this study was to investigate lidocaine disposition and bioavailability in rabbits after peroral and rectal administration. The peroral bioavailability in rabbits was found to be about 6 per cent and the rectal bioavailability is about 33 per cent. The results indicate that the rabbit is a suitable model for the study of systemic absorption of rectal lidocaine dosage fo

ISSN:0142-2782    

DOI:10.1002/bdd.2510060303

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractThe influence of protein‐calorie malnutrition (PCM) on the disposition of theophylline was investigated in male Sprague‐Dawley rats fed for four weeks on a 23 per cent (control) or 5 per cent (low) protein dietad lib.Dietary protein deficiency led to a decrease in body weight gain, plasma proteins. albumin, microsomal proteins, and cytochrome P‐450. After intravenous administration of aminophylline equivalent to 10 mg kg−1theophylline, the average mean residence time (MRT) was 58 per cent higher in the protein‐deficient rats, while the total plasma clearance (CI) per kilogram of body weight and elimination rate constant (k) were decreased by 39 per cent and 45 per cent, respectively, when compared to rats on a normal protein diet. No significant difference was found in the two groups of animals with respect to the apparent steady‐state volume of distribution (Vss). The present results suggest that the mechanism responsible for the observed pharmacokinetic changes in the protein‐deficient rats is related to the reduced amount and/or activity of the hepatic mixed func

ISSN:0142-2782    

DOI:10.1002/bdd.2510060304

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractThe absorption, distribution, and excretion of bromocriptine were studied following oral and parenteral administration of non‐radioactive and14C‐labelled drug in the rat. Total radioactivity was measured in blood, tissues, and excreta by liquid scintillation counting while the parent drug was determined in plasma and selected tissues by radioimmunoassay. The pharmacokinetic observations were compared with the time course of drug‐induced hypothermia in cold‐room acclimatized rats. The results indicated that oral doses of bromocriptine were rapidly, though incompletely (32‐40 per cent), absorbed, but underwent extensive first‐pass metabolism, resulting in an absolute bioavailability of only 6 per cent. The bioavailability increased to approximately 22 per cent in rats pretreated with the hepatic microsome inhibitor proadifen, thus suggesting the liver as the principal site of biotransformation. Absorbed bromocriptine showed preferential distribution into the tissues, although no apparent accumulation of drug‐related material occurred in the body. The drug was eliminated almost exclusively by metabolism and biliary excretion into the faeces. Comparison of the pharmacodynamic and the pharmacokinetic profiles indicated a dose relationship between hypothermia and plasma bromocriptine concentrations but not total radioactivity levels. The hypothermic response was also intensified by proadifen pretreatment, thus confirming the parent drug as the pharmacologically active entity. It is believed that the previously reported delay in the onset of bromocriptine activity is not pharmacokinetic in nature, but is related to the properties of the receptors at the target site or to the pharmacologic events that result in the obs

ISSN:0142-2782    

DOI:10.1002/bdd.2510060305

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractPlasma concentration‐time data resulting from constant rate intravenous infusion may be analysed in two ways:1.Samples may be collected both during and after infusion and fit to an infusion model.2.Samples may be collected after infusion is complete and the data may be fit as an i.v. bolus.The purpose of this study was to contrast these two fitting procedures in terms of the accuracy of the parameter values obtained. Concentration‐time data were computer‐generated with the introduction of random error to simulate the disposition profiles of two model drugs. The results of these simulations indicate that satisfactory values for area‐dependent parameters may be obtained without fitting data during the infusion phase. The exception to this is the apparent steady‐state volume whose values become less accurate with longer infusion times. The parameters most affected by ignoring data points in the infusion phase are the central volume of distribution, and the coefficient and disposition rate constant associated with the initial, rapid phase of disposition. The equation which describes the entire concentration‐time profile provides the most accurate parameter estimates of the model equation. In addition, we also describe the influence of the fitting method on the intercompartmental transfer rat

ISSN:0142-2782    

DOI:10.1002/bdd.2510060306

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractThein vitromicrobial degradation and the urinary excretion and biliary secretion in rats of two anthraquinone glycosides (sennosides A and B) and four aglycones (sennidins A and B, rhein, and danthron) were studied using a high performance liquid chromatographic system with gradient elution and amperometric detection. Microbial degradation of sennosides A and B occurred almost exclusively in the presence of mice caecum inoculae and was associated with the release of sennidins A and B. Rhein and danthron were indiscriminately metabolized by bacteria sampled from all regions of mice intestine, whereas sennidins lacked stability in biological media. The fraction of the dose administered orally to rats and recovered as aglycones or as glucuronides in bile and urine after 48 hours was five times greater for rhein (15 per cent) and danthron (13.4 per cent) than for sennosides A (1.8 per cent) and B (2.8 per cent) excreted or secreted as sennidins. These results support the concept that anthraquinone glycosides are less likely to enter the systemic circulation and, thus, are able to exert their laxative effect at lower doses than aglycones.

ISSN:0142-2782    

DOI:10.1002/bdd.2510060307

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510060308

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510060309

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510060310

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510060311

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY