Angiotensin-converting enzyme. Investigation of diurnal variation, the effect of a large dose of prednisolone, and prednisolone pharmacokinetics in patients with sarcoidosis.

Serial assay of serum angiotensin-converting enzyme concentrations (SACE) is advocated for monitoring disease progress in sarcoidosis. Because little is known of nondisease factors affecting SACE, 10 patients with histologically proved sarcoidosis were assessed for diurnal fluctuation in SACE and as to whether a large dose of corticosteroid had an immediate effect on SACE independent of disease. The pharmacokinetics of prednisolone in 8 of these patients was also evaluated. On Day 1, serum samples were obtained for 24 h after placebo, and the next day at the same times after 75 mg of orally administered prednisolone. There was no obvious diurnal pattern on either day, and there was no significant difference in SACE after prednisolone. The mean maximal difference obtained within or between days was 8.8%. Prednisolone pharmacokinetics were comparable to normal volunteers. SACE concentrations can be confidently determined at any time of day, and changes of greater than 9% are probably significant. The use of prednisolone in patients with sarcoidosis can be safely based upon pharmacokinetic data obtained from normal volunteers.

The effect of diet upon serum concentrations of theophylline.

Eight patients with airways obstruction were investigated to determine if dietary components had any significant effect upon serum concentrations of theophylline when taking a slow release formulation. A high carbohydrate, low protein diet, given for 1 week, resulted in the area under the concentration time curve for 12 h being 33.3% greater than a high protein low carbohydrate diet given under the same conditions. In contrast to two previous studies no significant effect upon the elimination half-life was detected after changing from one diet to the other and an effect of dietary components upon absorption and/or distribution needs to be considered. Morning and afternoon trough levels were significantly different from each other on both diets suggesting that theophylline kinetics are different at night. Individualising of theophylline dosing is particularly needed when treating patients on a varied dietary intake.

Slow release theophylline in patients with airways obstruction with particular reference to the effects of food upon serum levels.

Eighteen patients with airways obstruction were given slow release theophylline and were then investigated to determine the influence of a standard meal upon the serum levels achieved over the ensuing 12-hour period. After food the peak to trough differences were decreased and the serum levels were significantly lower over the first 6 hours. In this study, the patients were given 10 mg/kg/day of slow release theophylline and none subsequently was found to have toxic levels, therefore this was considered to be a reasonable dose with which to initiate therapy in adults with uncomplicated airflow limitation. However even under the strictly controlled conditions of the study there were wide variations between individuals in the blood levels achieved and serum monitoring is necessary to use theophylline in an optimal fashion.

Alveolar proteinosis: diagnosis and treatment over a 10-year period.

Ten years' experience of using bronchoalveolar lavage in the treatment of 10 patients with alveolar proteinosis is reported. The diagnosis was often missed. The interval between onset of symptoms and diagnosis varied from six weeks to six years (median 2 years), so that the start of treatment was often delayed. Some patients experienced severe progressive disability before they had treatment. Whole-lung lavage proved to be a safe, repeatable procedure which provided symptomatic, physiological, and radiological improvement and allowed all 10 patients treated to return to full-time employment.

Rifampicin reduces effectiveness and bioavailability of prednisolone.

Rifampicin is an inducer of hepatic drug metabolising enzymes. This results in interactions with several drugs including oral anticoagulants, hypoglycaemics, and contraceptives. Concurrent treatment with prednisolone and rifampicin is given when tuberculosis coexists with a disease that is sensitive to steroids, when the diagnosis is uncertain, or occasionally in the treatment of severe tuberculosis. Two patients with respiratory disease were treated with both drugs: their condition improved considerably after rifampicin was withdrawn. Seven patients were then studied to assess the effect of rifampicin on the pharmacokinetics of prednisolone. Overall, rifampicin increased the plasma clearance of prednisolone by 45% and reduced the amount of drug available to the tissues (area under the plasma concentration time curve) by 66%. The effectiveness of prednisolone may be considerably reduced when rifampicin and prednisolone are used in combination.

Cryptogenic organizing pneumonitis.

Eight patients with histological intra-alveolar organization, but no evidence of an infective or other aetiological agent, are reported. They characteristically presented with a short history of severe dyspnoea, cough, malaise, weight loss, bilateral radiographic shadowing and a raised ESR. There was a dramatic response clinically and radiologically to prednisolone but relapse occurred quickly as the dose was reduced. Control was re-established with an increased dose of prednisolone. In order to avoid confusion with post-infective organizing pneumonia the term cryptogenic organizing pneumonitis is suggested.

Comparison of radioimmunoassay and thin layer chromatographic assay methods for estimation of plasma prednisolone concentrations.

Radioimmunoassay and thin layer chromatographic methods of assay for prednisolone in plasma have been compared. These methods are comparable in terms of ease, speed of execution, and cost. They yielded similar estimates of prednisolone concentration without important bias over the concentration range generally encountered in clinical practice and may be considered comparable for pharmacokinetic studies.

Pharmacokinetics of prednisolone in normal and asthmatic subjects in relation to dose.

The pharmacokinetics of prednisolone have been studied in asthmatic patients following intravenous injection at three different doses and in normal volunteers at five oral doses. Plasma prednisolone concentrations were measured by radioimmunoassay. With increasing dose there is an increase in the apparent volume of distribution, plasma clearance and half life. The relationship between area under the plasma concentration time curve, maximum concentration and dose is linear but the regression lines do not pass through the origin. These findings following oral and intravenous administration confirm that prednisolone shows non-linear kinetics.