ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

摘要:

Phenytoin (diphenylhydantoin) is still the most commonly used anticonvulsant drug. It has certain physicochemical characteristics which make it liable to bioavailability problems. Due to the dose dependent metabolism of phenytoin and to its narrow therapeutic range even small changes in the bioavailability can cause major changes in serum phenytoin concentration and have serious clinical consequences.Numerous studies have demonstrated that there are products in general use with considerable differences in their bioavailability.If the epilepsy is well controlled, a change from one phenytoin product to another should be avoided. Such a change might lead to phenytoin intoxication or to poor control of epilepsy, if the products do not have the same bioavailability.There seems to be no systematic difference in the bioavailability of phenytoin sodium and phenytoin acid, if products of high quality are used. On the other hand, various biopharmaceutical factors, e.g. particle size of phenytoin and the nature of excipients in the product, can have a marked effect on the oral absorption of phenytoin. Gastrointestinal diseases, the concomitant use of other drugs and dietary factors might also modify the bioavailability of phenytoin. The absorption of intramuscularly given phenytoin is rather slow and erratic.The existence of phenytoin products with different bioavailability is a serious practical problem which should be corrected as soon as possible.

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

摘要:

It has previously been suggested that subjects who are initially slow metabolisers of drugs have a greater potential for induction of their drug metabolising enzymes than subjects with initial high rates of metabolism. This inference is based on observations made of changes in half-life of antipyrine. The purpose of this presentation is to reanalyse data previously presented in the literature with reference to clearance, a more precise estimate of drug metabolising activity, and half-life a parameter derived from both clearance and distribution.In one study in non-obese subjects, approximately 80% of intersubject variation in the change of total antipyrine clearance can be explained by differences in body size, particularly differences in liver volume. Furthermore, the relationship between initial antipyrine half-life and the percentage change in antipyrine half-life following induction can be explained by the association between each parameter and body weight. These observations imply that the potential for enzyme induction, and therefore for drug interactions based on enzyme induction, is present in all subjects and that intersubject variance in steady-state drug concentrations are as wide following induction as before induction.

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

摘要:

Prednisone and prednisolone are used in a wide variety of diseases. The two compounds are metabolically interconvertible; prednisolone is assumed to be the pharmacologically active species.Prednisone and prednisolone plasma concentrations are commonly determined by either radioimmunoassay or competitive protein binding techniques. No relationship has been demonstrated between prednisolone plasma concentration (unbound or total concentration) and clinical response; alternate day dosage regimens with fluctuating plasma concentrations being considered generally to be as effective with less side effects than a daily dosage regimen.Both drugs are rapidly absorbed after oral administration, reaching peak plasma concentrations after 1 to 3 hours. In general, plasma half-lives for prednisone are slightly longer (3.4 to 3.8h) than for prednisolone (2.1 to 3.5h). Either drug can be prescribed in most situations. On average, however, the bioavailability of prednisolone after oral prednisone is approximately 80% of that after prednisolone. A wide intersubject variation in prednisolone concentration is evident after both drugs, which may suggest impaired drug absorption in some individuals.Prednisolone shows dose dependent pharmacokinetics; an increase in dose leading to an increase in volume of distribution and plasma clearance. This can be explained in terms of the non-linear binding of the drug to plasma proteins. The degree of binding will determine the distribution and clearance of free (i.e. pharmacologically active) drug. Reduced doses are recommended in patients with hypoalbuminaemia.Prednisolone pharmacokinetics are also dependent on age; the half-life being shorter in children. Liver disease prolongs the prednisolone half-life and, due to the frequently associated hypoalbuminaemia, also increases the percentage of unbound drug. It has been recommended by some that prednisolone rather than prednisone is the drug of choice in active liver disease owing to the poor conversion of prednisone to prednisolone in some patients. However, the reduced plasma concentration of prednisolone in such patients is compensated for by delayed clearance. Thus, there is little advantage of one preparation over the other.Pharmacokinetic drug interactions have been reported, particularly accelerated clearance of prednisolone due to enzyme inducing agents such as barbiturates, phenytoin, rifampicin and other corticosteroids. On the other hand, oral contraceptives have been reported to increase the half-life and to decrease distribution volume and clearance of prednisolone, due to the increased levels of corticosteroid binding globulin (transcortin).

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

摘要:

20 routine patients with endogenous depression were investigated in a kinetic and 4 week treatment study. Steady-state plasma nortriptyline concentrations above 200μg/L were associated with a highly significant poorer therapeutic outcome.The correlations between the 24, 48 and 72 hour concentrations and steady-state concentration were very good (r = 0.81, 0.97, 0.94; p < 0.0001) and better than the correlation between half-life and steady-state (r = 0.65; p < 0.01). The Spearman rank correlations (Rs) between amelioration of depression measured by the Hamilton Rating Scale (HRS) and the 24, 48 and 72 hour concentrations were highly significant (Rs = 0.74, 0.79, 0.79; p < 0.001) but for half-life (Rs = 0.33) the correlation was not significant.The single 48 hour plasma nortriptyline concentration following a single oral dose is recommended as a reliable simplified monitoring test suitable for a busy clinic. The test is useful for dosage adjustment to maximise antidepressant action and minimise toxicity. A tentative dosage adjustment schedule for individualising antidepressant treatment with nortriptyline based on the 48 hour or the 24 hour plasma concentration is proposed.

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

摘要:

Acetylsalicylic acid in daily doses from 3 to 6g was prescribed to 8 patients with rheumatoid arthritis. Various assessments of clinical effect, as well as steady-state plasma concentrations and degree of plasma protein binding, were determined at each dose. The unbound fraction of salicylate increased with the dose, resulting in very high free concentrations of drug in some patients. No statistically significant relationship between total or unbound plasma concentration and the measurements of clinical efficacy were obtained. The marked increase with the dose in unbound salicylate concentration is interpreted as the result of the saturable elimination known to occur for this drug.

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

摘要:

The influence of renal failure and of hepatic cirrhosis on the plasma protein binding of etomidate, an intravenous anaesthetic agent of basic nature, has been investigated. The percentage of free etomidate in plasma containing 1 &mgr;g/ml was markedly increased in patients with renal failure and in patients with hepatic cirrhosis, when compared with a group of healthy volunteers (43.4 ± 2.9% and 44.2 ± 2.1 versus 24.9 ± 1.4%). This decrease in binding correlated inversely with serum albumin levels in both conditions (r = -0.88 and r = -0.72, respectively) but a slight decrease in the amount bound per mole of albumin was also apparent in both types of disease.

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS