Biomedical subjects
Publications and source records attributed to D N Bateman.
An accurate, rapid and repeatable technique of volume measurement is described; the equipment comprises a linear array scanner, a support gantry, a video tape recorder and an inexpensive microcomputer. The technique is being used to study gastric emptying but applications to other viscera, soft tissue masses and the fetus are possible.
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1 The effects of domperidone (20 mg) i.v. and saline i.v. on gastric emptying of 500 ml of fluid have been compared in a blind study in six normal male volunteers. 2 Gastric emptying was measured by real-time ultrasound. 3 Domperidone significantly reduced the volume in the stomach 5 min after the drink (domperidone 306 +/- 17 ml, saline 404 +/- 31 ml, P less than 0.02). 4 Domperidone had no significant effect on the half-life of gastric emptying measured between 5 and 60 min (T1/2 domperidone 21.2 +/- 1.17 min, T1/2 saline 21.3 +/- 1.58 min). 5 A similar pattern of gastric emptying to that produced by domperidone could be produced by giving a drink of a smaller volume.
1. The effects of meal temperature and volume on the emptying of liquid meals have been studied in eight normal volunteers. Four drinks were investigated: (i) 200 ml, 12 degrees C, (ii) 200 ml, 37 degrees C, (iii) 500 ml, 12 degrees C, (iv) 500 ml, 37 degrees C. Gastric emptying was measured by real-time ultrasound. 2. After an initial rapid phase of emptying, measured by the volume retained in the stomach at 5 min, emptying was mono-exponential and measured as a half-life. 3. The 5 min gastric volume was significantly reduced by giving a cold drink of 500 ml (12 degrees C: 250 +/- 33.1 ml. 37 degrees C: 307 +/- 25.8 ml, P less than 0.05). Temperature had no significant effect on the subsequent half-life of emptying. 4. The half-life was longer for meals of larger volume; at 37 degrees C this was statistically significant: 200 ml: t 1/2 7.6 +/- 2.1 min; 500 ml: t 1/2 15.3 +/- 2.8 min; P less than 0.01. 5. There was a significant positive correlation between the 5 min volume and the subsequent half-life of emptying for all meals except 200 ml at 12 degrees C, suggesting that resting gastric muscle tone affects both phases of gastric emptying. 6. Significant correlations within subjects for 5 min volume measurements for meals of different volume and temperature and half-lives of meals at 37 degrees C suggests that individuals have their own characteristics of gastric emptying for liquid meals.
The investigation examines the hypothesis that metoclopramide-induced potentiation of gastrointestinal motility is mediated through dopamine receptors. In vitro studies on the longitudinal muscle of the guinea-pig ileum were performed. Metoclopramide, in concentrations comparable with those seen in plasma after therapeutic doses in man, selectively potentiated the cholinergic response Dopamine (1-100 microM) inhibited cholinergic transmission by inhibiting neuronal acetylcholine release. The inhibitory action of dopamine was antagonised by phentolamine, and alpha-adrenoceptor antagonist, but not by the dopamine receptor antagonists metoclopramide or primozide. Bromocriptine inhibited cholinergic responses by a postsynaptic mechanism which was not antagonised by metoclopramide, primozide, or phentolamine. The results are consistent with the view that metoclopramide-induced potentiation of gastrointestinal motility does not involve local dopamine receptors.
A safe non-invasive technique for the measurement of gastric volume by real-time ultrasound is described. The application of this technique to the measurement of the emptying of liquid from the stomach is outlined. Gastric emptying of liquid was found to be log-linear, the mean half-life of emptying in 10 volunteers being 22 . 0 +/- 2 . 5 min. Ultrasound measurement of gastric emptying provides an opportunity to study the effects of drugs and disease on gastric motor function in man.
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The pharmacokinetics of metoclopramide have been studied after intravenous and oral dosing (10 mg) to 6 patients with chronic renal failure. The mean terminal half-life was 13.9 h after intravenous and 14.8 h after oral administration. Total body clearance after i.v. dosing was 16.7 l/h. Oral bioavailability was 71.8%. In comparison to previous studies on normal subjects these results indicate that clearance of metoclopramide in renal failure is approximately 30% of normals. This difference is not accounted for by the change in renal clearance and suggests impaired metabolism or an alteration in enterohepatic circulation of metoclopramide in renal failure.
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1 The pharmacokinetics of metoclopramide have been studied in eight normal male volunteers. 2 The mean plasma beta half-life was 156.7 min after i.v. administration of 10 mg metoclopramide. 3 After oral dosing of 10 mg the mean half-life was 196.6 min and after 20 mg 317.5 min (P less than 0.05). 4 Bioavailability of a 10 mg oral dose of metoclopramide varied between 32 and 97%. 5 A major urinary metabolite was metoclopramide-N-4-sulphate and the amounts of conjugates appearing in urine to 24 h correlated significantly with the bioavailability. 6 In the dog the metabolic fate of metoclopramide is different to man with conjugation being a minor metabolic pathway. The half-life in the dog does not appear to be dose dependent. 7 The wide differences in bioavailability of metoclopramide in man may contribute to the unpredictable occurrence of side effects.
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The pharmacokinetics and effects of prazosin have been studied after intravenous and oral dosing (1 mg) to 6 normal male volunteers. The mean terminal (beta) half-life was 2.9 h after intravenous and oral routes. Oral bioavailability was 56.9%. The effects of prazosin on blood pressure were more pronounced after intravenous than oral administration, and the hypotensive effect greater on erect blood pressure. There was a significant correlation (P less than 0.02) between the fall in blood pressure and the plasma drug concentration after intravenous prazosin.
1 The hypotensive effect of single daily dosing with atenolol 100 mg and chlorthalidone 25 mg given alone or in combination has been assessed in a double-blind, crossover, placebo controlled trial in fifteen hypertensive patients. 2 Average lying blood pressures were: Placebo 155.4/103.9 mm Hg, atenolol 134.6/85.8 mm Hg, chlorthalidone 139.5/90.1 mm Hg, combination 127.7/82.5 mm Hg. 3 The effect of the combination therapy in reducing lying diastolic pressure compared with placebo (a fall of 21.4 mm Hg) was significantly less than the 31.9 mm Hg fall predicted from the sum of the individual effects (P = 0.01). 4 Observations on blood pressure at rest and under mental, isometric and bicycle ergometer stress were made pre-dose and post-dose for a 12 h period at the end of the last treatment period. 5 Lying blood pressure declined from the zero hour (pre-dose) reading on all treatments to a low at 15.00--18.00 h and then rose again. 6 The rise in systolic blood pressure after isometric exercise and mental stress was of a similar magnitude with all four treatment regimes. 7 Atenolol, alone and in combination with chlorthalidone, reduced the blood pressure and the pulse rate increase on exercise 2 h post-dose when compared with readings 24 h post-dose. 8 Once daily dosing with a combination of atenolol and chlorthalidone produced a fall in supine blood pressure over a 24 h period but the effect on exercise induced changes was not uniform over this period.
1 The effects of single oral doses of 10 mg and 20 mg metoclopramide have been compared to placebo in six normal male volunteers. 2 The drug did not significantly increase the rate of gastric emptying as measured by ethanol absorption. 3 Sedation during the absorption of ethanol was only observed 1 h after the 20 mg oral dose of metoclopramide (P less than 0.05). 4. Akathisia, a central nervous system side effect of metoclopramide, occurred only in subjects who had peak plasma concentrations above 100 ng/ml. 5 It has not been possible to define a concentration-effect relationship for the action of metoclopramide on the stomach and comparison with previous results after intravenous dosing suggests that the route of administration is of major importance in determining the action of this drug.