Search

Blood concentrations of promethazine and promethazine sulphoxide have been measured following oral and intravenous administration of promethazine to seven healthy male volunteers. Promethazine disposition is characterised by a large volume of distribution (1970 1) and a high blood clearance (1.141 min-1). Less than 1% of the dose is excreted unchanged in the urine, therefore total body clearance is essentially metabolic clearance. In accord with this high clearance the oral availability of promethazine is only 25%. The absorption of promethazine from the gastrointestinal tract exceeds 80% in most subjects. Minimal metabolism by the gastrointestinal mucosa is implicated. Promethazine sulphoxide pharmacokinetics are consistent with a pronounced first pass effect. Although the area under the curve for this metabolite is not route dependent, there is a marked alteration in the shape of the metabolite curve when oral and intravenous data are compared. Evidence is presented to support the hypothesis that S-oxidation of promethazine is predominantly an hepatic event. The conclusions of previous investigators with regard to the role of the gut mucosa in S-oxidation of phenothiazines is critically assessed.

Total body pool and intestinal absorption of ascorbic acid were studied in 12 patients undergoing operation for Crohn's disease (six with fistulae and six without) and in six control patients undergoing operation for reasons other than Crohn's disease. L-[carboxyl-14C]Ascorbic acid, 0.19-0.40 megabecquerels (MBq), was given orally. After a period of equilibration, the labeled ascorbic acid was flushed out of the patient's body tissues using large doses of unlabeled ascorbic acid. Intestinal absorption of ascorbic acid, assessed from the total cumulative urinary 14C recovery, was found to be similar in patients with fistulizing Crohn's disease (73.9 +/- 8.45%), those without fistulas (72.8 +/- 11.53%), and in controls (80.3 +/- 8.11%). Total body pools of ascorbic acid, calculated using the plasma 14C decay curves, were similar in patients with Crohn's disease with fistulas (17.1 +/- 5.91 mg/kg), patients without fistulas (9.6 +/- 3.58 mg/kg), and in controls (13.3 +/- 4.28 mg/kg). The results indicate that ascorbic acid absorption is normal in patients with both fistulizing and nonfistulizing Crohn's disease. The results suggest that routine supplements of vitamin C are not necessary unless oral ascorbic acid intake is low.

The pharmacokinetics of metronidazole were studied after oral and intravenous administration to seven patients with Crohn's disease and five patients with ulcerative colitis. The oral/intravenous availability ratio was 0.97 +/- 0.2 in the Crohn's patients and 0.90 +/- 0.1 in the colitics (mean +/- s.e. mean). Plasma clearance was 3.24 +/- 0.2 l h-1 and 4.1 +/- 0.5 l h-1, respectively. These differences were not statistically significant. Ten of the patients on long term sulphasalazine were studied to observe the effect of 2 weeks metronidazole therapy on plasma sulphapyridine concentration. The sulphapyridine concentration changed from 22.1 +/- 2.0 micrograms ml-1 to 15.95 +/- 4.5 micrograms ml-1 in the Crohn's patients and 26.0 +/- 6.0 micrograms ml-1 to 36.4 +/- 8.5 micrograms ml-1 in the colitis group, pre- and post-metronidazole. These differences were not statistically significant. These results suggest that metronidazole does not interfere with diazo-link splitting of sulphasalazine and that patients with Crohn's disease handle metronidazole in a similar manner to patients with colitis.

An easy-to-use interactive program (QUEST) has been developed which facilitates the input, updating and checking of patient records from completed questionnaires possibly destined for statistical analysis by SPSS. Using the information about the data available in the SPSS control file, blank questionnaires can be generated, and up to date completed questionnaires printed. Selected cases can be printed out. QUEST is currently being used in four medical studies and one legal study. The program is written in standard Fortran-77 and makes full use of the new features of the language.

We pursued the possibility that Mycobacterium kansasii might be an aetiological agent in Crohn's disease by carrying out a trial of treatment with antimycobacterial drugs. Twenty seven patients with Crohn's disease took part in a two year randomised double blind, crossover, controlled trial of rifampicin plus ethambutol against placebo. Fourteen patients completed the trial; four required an operation; five were withdrawn as poor compliers, and four because of adverse effects. There was no significant difference in response to the active drugs compared with placebo when expressed in terms of a Crohn's disease activity index or any clinical indicator of disease activity. There was no suggestion that any subgroup of patients - for example, different regions of bowel affected or previous operation - were favourably affected by the drugs. There was no consistent pattern of change in prednisolone requirements although eight patients on long term sulphasalazine had a significant reduction in their plasma sulphapyridine concentrations during the active treatment period. A significant reduction in total white blood count and an increase in plasma ALT were seen during active therapy. The results of the study do not suggest that rifampicin and ethambutol have a role to play in the treatment of Crohn's disease.