ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Part I of this article, which appeared in the previous issue of the Journal, covered the following agents: histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine); muscarinic-M1-receptor antagonists (pirenzepine); proton pump inhibitors (omeprazole); site-protective agents (colloidal bismuth subcitrate, sucralfate); antacids and prostaglandin analogues; antiemetics and prokinetics (metoclopramide, domperidone, cisapride); and antispasmodics. In Part II, we consider the anti-inflammatory salicylates, nonspecific antidiarrhoeal agents, laxatives and cathartics.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

The growth of knowledge in the field of the pharmacokinetics of prednisolone/prednisone has been slow for several reasons. First, convenient and specific methods for measuring these steroids only became available with the development of high performance liquid chromatographic methods. Secondly, prednisolone is nonlinearly bound to transcortin and albumin: since the unbound concentrations of prednisolone are biologically relevant, it was necessary to determine the free fraction in each plasma sample. Thirdly, due to the short half-life of prednisolone no steady-state is achieved, and therefore area under the concentration-time curve needed to be determined in all studies. Fourthly, prednisolone and prednisone are interconvertible and prednisolone is given intravenously as an ester prodrug, features which created controversies about the correct interpretation of pharmacokinetic results. Finally, the total body clearances of total and (to a lesser degree) of unbound prednisolone increase with increasing concentrations of prednisolone. Therefore, in order to compare pharmacokinetic results between different subjects, standardised doses had to be administered.The investigations performed so far have revealed that: (1) the dose-dependent pharmacokinetics partly explain the clinical observation that an alternate-day regimen with prednisone yields fewer biological effects; (2) the interconversion of prednisone into prednisolone is not a limiting factor, even in patients with severely impaired liver function; (3) hypoproteinaemiaper sedoes not cause increased unbound concentrations of prednisolonein vivo;(4) patients with liver failure, renal failure or a renal transplant, subjects older than 65 years, women on estrogen-containing oral contraceptive steroids or subjects taking ketoconazole have increased unbound concentrations of prednisolone - whereas hyperthyroid patients, some patients with Crohn's disease, subjects taking microsomal liver enzyme-inducing agents or patients on intravenous prednisolone phthalate (instead of prednisolone phosphate) or on some brands of enteric coated prednisolone tablets have decreased concentrations of prednisolone. The biological relevance of the altered pharmacokinetics is supported in part by altered clinical effects and altered effects on cellular immunofunctions.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Many diseases appear to lead to a decrease of drug plasma binding due either to hypoalbuminaemia or to a modification of albumin structure. In other diseases, the binding of a drug may increase due to elevated concentrations of &agr;1-acid glycoprotein or lipoproteins. However that may be, the free fraction of a drug may vary in different pathologies. But an increase or decrease of the drug free fraction does not automatically mean an increase or decrease of the free drug concentration. Whatever the drug, a variation in the volume of distribution more or less proportional to the variation in the plasma free fraction can be expected. With respect to the clearance, the problem is much more complex and depends on the hepatic extraction ratio of drug. If the extraction is related to the free fraction (fu) of drug, a variation in fuwill lead to a variation in the total drug concentration but no variation in the free drug concentration and no change in the pharmacological effect. If the extraction of a drug is dependent on hepatic flow, a variation in fuwill lead to a change in the free drug concentration (with no change in the total drug concentration) and hence changes in the pharmacological effect.The aim of this article is to review the literature concerning disease-induced variations in plasma protein levels during the past 10 years. Finally, possible implications for drug dosage regimens are discussed generally from examples studied in the literature.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

The pharmacokinetics of ketanserin, a new serotonin S2(5HT2) antagonist, were studied in 26 patients with cirrhosis. Patients were randomised to receive either a single oral dose of ketanserin 20mg (n = 14) or 40mg (n = 8) or an intravenous dose of ketanserin 5mg (n = 4). The plasma kinetics of ketanserin and its metabolite ketanserinol were determined over 48 hours, by high pressure liquid chromatography with a fluorometric detector. Pharmacokinetic parameters were calculated using noncompartmental analysis based on a statistical moment theory. The first-pass effect of ketanserin was markedly decreased after oral administration compared with results previously obtained in healthy subjects. The peak concentration was not higher in cirrhotic patients than in controls. This result could be due to an increase in the initial volume of distribution. The production of ketanserinol was reduced in cirrhotics. A decreased mean ketanserin elimination half-life (t½= 12 ± 4 and 10 ± 3hvs16 ± 3 and 18 ± 4h in healthy controls after oral ketanserin 40mg and intravenous ketanserin 5mg, respectively) contrasted with a substantial increase in t½for ketanserinol (33 ± 13vs19 ± 4h). The volumes of distribution were also markedly reduced in patients with cirrhosis. These results suggest either a reduction in the oral dosage of ketanserin or an increase in the interval between doses in patients with cirrhosis.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

The authors observed an interaction between allopurinol and both theophylline and warfarin in 2 patients. To determine the possible effect of allopurinol on hepatic oxidative metabolism a [14C]-aminophenazone (aminopyrine) breath test was performed before and during treatment with allopurinol 100mg daily in 5 patients with hyperuricaemia. Allopurinol prolonged the [14CO2]-aminophenazone half-life from 72 ± 13 to 104 ± 16 minutes (mean ± SEM, p < 0.05). It is possible that allopurinol may produce clinically significant drug interactions through an inhibitory effect not only on xanthine oxidase metabolism but also on oxidative metabolism.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS