Gastroenterology Unit and Department of Clinical Pharmacology, Royal Victoria Infirmary and University of Newcastle upon Qne. Newcastle upon Qne, U.K..
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Clinical Science (1982) 63,81-85
Propranolol absorption in untreated coeliac disease
G. I . S A N D L E , A . W A R D , M. D . R A W L I N S A N D C . 0. R E C O R D Gastroenterology Unit and Department of Clinical Pharmacology, Royal Victoria Infirmary and University of Newcastle upon Q n e . Newcastle upon Qne, U.K.
(Received 21 October 1981; accepted 29 January 1982)
Summary 1. To compare the bioavailability and the elimination of propranolol in seven untreated coeliac patients and six normal subjects, plasma concentrations were measured after oral and intravenous propranolol. The bioavailability and clearance of propranolol were similar in both groups. 2. With the use of a perfusion technique, propranolol absorption in the proximal jejunum was found to be decreased by 71% in five untreated coeliac patients, compared with the absorption in four normal subjects. 3. These results indicate that propranolol absorption is decreased in the proximal jejunum in untreated coeliac disease but overall absorption in the small bowel is not impaired.
Key words: absorption, coeliac disease, jejunum, propranolol. Abbreviations: AUC, area under curve. Introduction
After oral administration, higher plasma propranolol concentrations have been observed in patients with coeliac disease than in normal subjects [ 1,21. Although the coeliac patients were in remission, higher plasma concentrations were attributed to a combination of faster absorption across their abnormal proximal jejunal mucosa and saturation of first-pass extraction by the liver [ll. Similar results were also obtained in untreated coeliac patients, although plasma proCorrespondence: Dr C. 0. Record, Gastroenterology Unit, Royal Victoria Infirmary, Newcastle upon Tyne NE14LP, U.K.
pranolol concentrations were only significantly greater than controls at If h and at peak values 131. Since propranolol is lipid soluble [41 and absorbed by passive diffusion, propranolol absorption in the proximal jejunum might be expected to be impaired in untreated coeliac disease, where the mucosal area available for absorption is diminished. Therefore, in order to investigate further the kinetics of propranolol absorption in coeliac disease, we have compared plasma propranolol concentrations after oral and intravenous administration in patients and controls, and measured segmental absorption of propranolol in the proximal jejunum by using an intestinal perfusion technique. Methods
After giving their informed consent, seven patients (six female; mean weight 47-9 f SE 2.2 kg, mean age 37 f 7 years) with coeliac disease, presenting with diarrhoea, weight loss and subtotal or total villous atrophy on jejunal biopsy, were studied before starting a gluten-free diet. Six healthy females (mean weight 49.9 f 4.0 kg, mean age 40 f 8 years) with functional bowel disturbance but normal jejunal biopsies, acted as controls. Table 1 shows the jejunal biopsy findings and the results of the routine haematological tests performed in each group of patients; barium follow-through examinations of the small bowel were normal in the controls. Oral and intravenous studies were performed randomly on successive days. Propranolol (40 mg) was administered orally after a 9 h fast and blood samples (20 ml) were obtained before and f, 1, 14, 2, 3, 4, 6 and 8 h after, via a cannula inserted into a forearm vein and kept patent with sodium chloride solution (154 mmol/l :saline)
0143-5221/82/07OO8 1-05SO1.50 0 1982 The Biochemical Society and the Medical Research Society
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G.I. Sandle et al. TABLE1. Results of histological and haernatological investigations in six control and seven coeliac patients STVA, Subtotal villous atrophy; TVA, total villous atrophy; ESR, erythrocyte sedimentation rate. ~~~~
~~
Patient no.
~~~
~
Sex
~
Weight (kg)
Jejunal biopsy
Haemoglobin
(years)
24 24 74 37 31 53
40.0 46.5 67.0 50.7 54.5 42.0
Normal Normal Normal Normal Normal Normal
13.7 12.5 15.1 13.7 14.7 12.6
63 67 21 17 27 34 35
55.5
42.5 47.0 42.0 53.5 50.0 43.5
STVA TVA TVA
13.3 12.3 9.7 13.5 11.3 11.8 12.5
Age
(g/dl)
Mean corpuscular volume (fl)
Control patients 1
F
2 3 4 5 6
F
F F
F F
Coeliac patients I 2 3 4 5 6 7
M F F
F F F F
STVA TVA STVA TVA
Normal range
13.5-18.0 (male) 11.5-16.3 (female)
ESR (mm/h)
84 91 84 88 88 87
-
88
16
I10
6
68 84 92 I10 106 77-100
6 32' 2 I 16
8 -
12 10 15
(20 (male)
