1. Propranolol and folic acid absorption were studied separately in healthy subjects, non-coeliac patients and patients with treated and untreated coeliac disease. 2. The surface pH of jejunal biopsy samples was measured with a pH electrode. 3. When compared with values found in healthy subjects, plasma propranolol levels were elevated in coeliac disease and, in contrast, serum folic acid levels were depressed after oral administration of the drug. Jejunal surface pH was more alkaline in the coeliac groups than in the healthy and non-coeliac subjects. 4. Pharmacokinetic analysis of the plasma drug levels allowed evaluation of the rate constants associated with absorption and elimination. The absorption rate constant was decreased for folic acid in the coeliac group, but increased for propranolol. These changes correlated with variation in surface pH. 5. Although the changes in drug disposition in treated and untreated coeliac disease are the result of several factors, it is suggested that jejunal surface pH may affect the rate of absorption and therefore the plasma concentration-time profile of drugs which undergo dissociation.
1. The plasma propranolol concentrations after a single oral dose of 40 mg were measured in 25 patients with rheumatoid arthritis and compared with those of 16 patients with Crohn's disease from a previous study. Thirteen healthy volunteers were used as controls. 2. In both diseases some high and some low values occurred. This scatter did not correlate with any symptoms or biochemical or haematological data other than with the erythrocyte sedimentation rate (ESR). 3. Both sets of patients were therefore separated into two groups depending on whether or not their ESRs were above or below 20 mm/l h. In both diseases the plasma propranolol concentrations of the patients with a raised ESR were significantly higher than the controls as well as those of the low ESR group. 4. In rheumatoid arthritis the plasma propranolol concentrations of the patients with a low ESR did not differ from those of the controls, but in Crohn's disease they remained significantly higher. 5. In one patient with Crohn's disease there was a dramatic rise in propranolol concentrations during an exacerbation (ESR 91 mm/l h) compared with those during a remission (ESR 20 mm/l h). 6. A difference in smoking habits did not seem to have been responsible for the difference in plasma propranolol concentrations.
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