Clinical trial: oral prednisolone metasulfobenzoate (Predocol) vs. oral prednisolone for active ulcerative colitis.

BACKGROUND: Systemic corticosteroids are effective in ulcerative colitis but commonly cause side effects. AIM: To compare the safety and efficacy of a sparingly absorbed formulation of prednisolone metasulfobenzoate (Predocol) with a conventional tapering course of oral prednisolone. METHOD: In a double-blind randomized study, 59 active ulcerative colitis patients received Predocol 40 mg/day for 6 months, 61 received Predocol 60 mg/day for 6 months and 61 received prednisolone 40 mg/day for 2 weeks, tapered to week 8, followed by placebo until 6 months. RESULTS: Steroid-related side effects assessed using a 10-cm visual analogue scale were fewer at 2 months with Predocol 40 mg [VAS 8.1 cm (2.6), mean (s.d.)], or 60 mg [8.1 (2.1)] compared with prednisolone [6.7 (2.7); P = 0.01]. Mood changes affected 43% receiving prednisolone at 4 weeks vs. 8% for Predocol 40 mg (P = 0.001). Remission rates (Powell-Tuck < or =2) at 2 months were Predocol 40 mg 46%, Predocol 60 mg 28% and tapering prednisolone 41% (P = 0.13). Visual analogue scale for efficacy also showed non-inferiority for Predocol 40 mg/day. Remission rates at 6 months were Predocol 40 mg 51%, Predocol 60 mg 38% and tapering prednisolone 32% (P = 0.08). CONCLUSION: Predocol 40 mg/day has similar efficacy but markedly fewer side effects than a conventional tapering prednisolone regimen (ISRCTN14133410).

The effectiveness of external beam radiotherapy for acromegaly is not affected by previous pituitary ablative treatments.

Thirty-three acromegalic patients were treated with radiotherapy and followed up for at least 3 years (mean 6 years, range 3 to 12). Seventeen had not had previous pituitary ablative therapy and 16 had. The mean GH level for these two groups before radiotherapy was comparable at 98 and 119 mIU/l. The observed frequency of reaching less than 10 mIU/l was 53% and 75% of patients in the two groups, respectively, the mean observed falls in growth hormone level were 81 and 85% of the initial level, and the calculated exponential decline rate of GH level was 72 and 52% per year. Considering all 35 patients, requirement for pituitary hormone replacement therapy increased from 15 patients before radiotherapy to 20 after radiotherapy, being mostly those who had had prior ablative therapies. There were no complications attributable to the radiotherapy treatment. It appears that radiotherapy is equally efficacious whether a prior unsuccessful ablative procedure had been used or not.

Debrisoquine oxidation phenotype and susceptibility to lung cancer.

1. It has been suggested that poor metabolisers of debrisoquine are at reduced risk of developing lung cancer from smoking cigarettes. This has been investigated in 82 patients with established cancer of the lung. 2. The frequency of poor metaboliser subjects was not different from that in the normal population. 3. There was no tendency for subjects with lung cancer to metabolise debrisoquine more rapidly than non-cancer subjects. 4. It is concluded that debrisoquine metabolic phenotype is not a good predictor of risk of developing lung cancer in the population at large.

Comparison of the safety of several nonsteroidal anti-inflammatory drugs currently or formerly marketed in the United Kingdom.

Reports of suspected adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) were related to estimated numbers of prescriptions for these drugs during the years 1968 to 1981. The 16 drugs first marketed during this period had similarly high initial rates of adverse effects reported, followed by a rapid decline. There was a marked variation between drugs in initial reporting rates. A number of factors may confound comparisons between drugs and appeared to apply to two drugs: fenbufen, for which the numbers of reports was increased by reports from a postmarketing surveillance study, and zomepirac, which was labeled and tested as a general analgesic (i.e., differently from the other NSAIDs). Otherwise, the drugs with higher initial rates of reported adverse experiences later were withdrawn from the market. Naproxen and ketoprofen, which were marketed the same year (1973) and used continuously for over 14 years in the United Kingdom, were associated with similar reporting patterns that were different from those for many other NSAIDs. It is concluded that anomalies in the frequency and pattern of suspected drug-related adverse reactions in the absence of any confounding factor are an important signal of the need for further investigation.

Postmarketing surveillance of enalapril. I: Results of prescription-event monitoring.

To identify and measure the incidence of adverse effects of the angiotensin converting enzyme inhibitor enalapril 13,713 patients were studied for one year by prescription-event monitoring. Precise information about the duration of treatment was available for 12,543 patients. The frequency of many events was calculated, including dizziness (483 patients; 3.9%), persistent dry cough (360; 2.9%), headache (310; 2.5%) hypotension (218; 1.7%), and syncope (155; 1.2%). Less common reactions included angioedema, urticaria, and muscle cramps. Altogether 1098 (8%) patients died and the notes of 913 of them (83%) were obtained for detailed scrutiny. With the exception of a few patients with renal failure who deteriorated during treatment (reported on separately), no death was attributed to enalapril. Enalapril was considered to be effective, even in patients with advanced cardiac failure. These results for enalapril are reassuring and provide further evidence of the value of prescription-event monitoring.

Postmarketing surveillance of enalapril. II: Investigation of the potential role of enalapril in deaths with renal failure.

The possibility that enalapril might damage renal function was investigated in 1098 deaths recorded in a prescription-event monitoring study. Case notes for 913 patients were examined. In seventy five there was a rise in the urea or creatinine concentration of 50% or more above pretreatment values. Enalapril appeared to have contributed to a decline in renal function and subsequent death in 10 of these patients. Several characteristics were identified among these patients, including old age, the use of high dose or potassium sparing diuretics, and pre-existing renal disease. Adding a non-steroidal anti-inflammatory drug was also associated with a deterioration in patients with previously stable renal function. No death was encountered of a patient with uncomplicated hypertension. Enalapril infrequently contributed to a substantial decline in renal function in certain vulnerable patients, especially those receiving other drugs known to be capable of adversely affecting renal function. Awareness of the characteristics of these patients and of their concomitant treatment may serve to reduce the risk.

Quinidine and the identification of drugs whose elimination is impaired in subjects classified as poor metabolizers of debrisoquine.

Quinidine and its diastereoisomer quinine were tested in vitro for their effect on the 4-hydroxylation of debrisoquine, the O-deethylation of phenacetin and the 1'-hydroxylation of bufuralol, by human liver microsomal samples; quinidine was studied for its effect on debrisoquine 4-hydroxylation in vivo. Quinidine was a potent inhibitor of the 4-hydroxylation of debrisoquine and the 1'-hydroxylation of bufuralol, with IC50 values of 0.7 and 0.2 microM, being around 100 times more potent in this respect than quinine. Very much higher (1000-fold) levels of quinidine were required to inhibit the O-deethylation of phenacetin, being rather less potent in this than quinine. Eight subjects were phenotyped for their debrisoquine oxidation status and found to be extensive metabolisers (EM). They were tested again after the co-administration of 50 mg of quinidine with the debrisoquine. The concomitant administration of quinidine increased the metabolic ratios (MRs) by a mean of 26-fold. The effects of quinidine at a dose of only 50 mg, on the metabolism of a new drug in EM subjects may prove a useful method of assessing the contribution of the debrisoquine 4-hydroxylase isozyme to the elimination of the drug tested.

Pulmonary hypertension in hydralazine induced systemic lupus erythematosus: association with C4 null allele.

A patient who developed pulmonary hypertension and systemic lupus erythematosus as a complication of hydralazine therapy is reported. She was a slow acetylator and in addition was found to have a null allele at the C4A locus.