- Email: [email protected]
EFFECT OF ANTACIDS ON ABSORPTION OF CIMETIDINE
965 actlon
limit of 80
mg/dl divided by
the number of hours
since
mgestion. This gives a line which is very close to the suggested reference line. The maximum difference, 1 mg/dl at 10 h, is nell within the errors of the plasma-measurement and of the estimation of the time elapsed since the overdose. R. B. PAYNE St James’s University Hospital, P. SHERIDAN Leeds LS9 7TF
CYSTEAMINE INJECTION FOR PARACETAMOL POISONING
SIR,-Cysteamine, a drug not yet generally available, is used with success in patients severely poisoned with paracetamol (acetaminophen). However, stability of solutions of cystea2 mme has been a problem. 1 Injections of cysteamine hydrochloride have been prepared either as a freeze-dried product to be reconstituted in 5% dextrose immediately before use,3 or as freshly prepared solutions to be injected directly through a disposable Millipore filter attached to a syringe.4 The preparation of freeze-dried cysteamine for injection is time consuming and requires special equipment in the hospital pharmacy. Bacterial contamination after direct Millipore filtration is a real danger. We investigated samples of six commercially available cysteamine hydrochloride preparations.5 One of these substances had deteriorated to the extent of containing about 40% as the oxidation product, cystamine. A freeze-dried preparation for injection had deteriorated by about 20%. A stable injection can be prepared as follows. Cysteamine hydrochloride of a good quality is dissolved in ascorbic acid solution 11.5 mmol/1; after filtration the solution is filled into suitable vials or ampoules under nitrogen. The solution is sterilised by autoclaving in saturated steam at 1150C for 30 min. A stable ready-to-hand injection is then available.
displayed without adding VAR, and 4.2000 is the corwhen using the check figures. Other simple check figures give correct answers also. Omitting two ENT therefore shortens the program to 11 steps. There are likely to be alternative ways of programming several of the equations but certainly the shorter ways are preis in fact
rect answer
ferable. Department of Anæsthesia, Janeway Child Health Centre, St. John’s, Newfoundland A1A 1R8,
D. G. Ross
Canada
EFFECT OF ANTACIDS ON ABSORPTION OF CIMETIDINE
SiR,—The histamine H2-receptor antagonist, cimetidine, is effective treatment for peptic ulceration.’-’ Patients treated with cimetidine may also take antacids to relieve pain during the early period of treatment. Since some antacids, especially an
those containing aluminium hydroxide, may act as adsorbents and interact with drugs in the gastrointestinal tract to alter their absorption, we studied the absorption of cimetidine when it was administered alone or with an antacid. The study was done in six healthy subjects (two females, four males) aged 22-42 years. Each was studied on three occaBLOOD CONCENTRATIONS CIMETIDINE
(jg/mt):
MEAN:i:S.E.M.
Hospital Pharmacy, Regional Protestant Hospital,
J. R. B. J. BROUWERS
Bennekom, Netherlands
Hospital Pharmacy, Andreas Hospital, P.
Amsterdam
VERMEIJ
PROGRAMMABLE CALCULATORS
studied,
S)R,—I read with enthusiasm Dr Ross and Dr Manson’s article (Aug. 28, p. 446) since I own a ’Sinclair Scientific ProWhen I checked the alveolar air equawith the variables provided I consistently got the answer B=4.8333 instead of x=4.2000 suggested. The program printed contains an error. All programs should end with ... B tR:_cct otherwise the results of the final calculation will not
grammable’ calculator. tion
be
displayed.
The program could be reduced by two unnecessary ENT entries to read BE/STO/ENT/VAR/-/VAR/—/VAR/X/-/RCL/+/
KAr_E((12 steps). St Thomas’s House, St T homas’s Hospital Medical London SE1
School,
*/This letter has been shown
J. H. WEST to
Dr
Ross, whose reply fol-
lows.—ED. L.
SIR,-Mr West is quite correct in pointing out that the second and third ENT are unnecessary, but the final calculation
1 Prescott, L F, Newton, R. W., Swainson, C. P., A R W, Matthew, H. Lancet, 2 Heyst, v., A. N. P, Douze, J. M.
Wright N , Forrest, 1974, i, 588. C., Pikaar, S. A. Ned. T Geneesk. 1976,
120, 1151 3 Prescott, D. F, Park, J., Sutherland, G. R., Smith, I. J., Proudfoot, Lancet, 1976, ii, 109. 4 Douglas, P, A Hamlyn, A. N., James, O. ibid 1976, i, 111. 5 Brouwers, J R B. J , Vermeij, P. Pharm.Wkbl. 1976, 111, 204.
sions not less than 1 week apart. On one occasion, cimetidine 400 mg was taken alone with a breakfast consisting of orange juice, cereal, toast and marmalade, and coffee; this was repeated on the other two occasions but antacid was also taken at 6 P.M. and 10 P.M. on the previous evening, at 8.15 A.M. breakfast, and 30, 90, and 150 m after cimetidine. Two antacids were one was ’Rennie’ (2 tablets/dose) which is the antacid being used in many of the controlled clinical trials of cimetidine, the other was ’Aludrox SA’ (20 ml dose) containing aluminium hydroxide gel 4.75 ml and magnesium hydroxide 100 mg in each 5 ml. The order of treatment was randomised. Venous blood-samples were collected every 15 or 30 min for 4 h after dosing, and urine was collected for 24 h. Blood and urine cimetidine concentrations were estimated by high-pressure liquid chromatography. Blood data were analysed by Student’st test. The mean blood concentrations for five of the eleven times are shown in the table. No statistically significant difference in blood concentration of cimetidine was demonstrated between dosage regimens. There were no significant differences in urinary output of cimetidine between any of the regimens. The blood and urine concentrations of cimetidine obtained in this study indicate that the concurrent administration of cimetidine and antacids in the form of rennie and aludrox causes no alteration in the absorption and excretion of cimetidine. Rennie tablets
were
provided by Nicholas Laboratories Ltd.
Research Institute, Smith Klme & French Laboratories Ltd, Welwyn Garden City, Herts
H , Stekelman, M., Milton-Thompson, G. J., MisJ Lancet, 1976, i, 337 2. Haggie, S. J , Fermont, D C., Wyllie, J. H. ibid p. 983. 3. Blackwood, W S , Maudgal, D P., Pickard, R. G., Lawrence, D , North-
1.
Pounder,
R. S , Hunt, R.
iewicz, J
A. T
W. L. BURLAND D. W. DARKIN M. W. MILLS
field, T C ibid 1976, ii, 174 G., Walan, A ibid. p. 161.
4. Bodemar,
limit of 80
mg/dl divided by
the number of hours
since
mgestion. This gives a line which is very close to the suggested reference line. The maximum difference, 1 mg/dl at 10 h, is nell within the errors of the plasma-measurement and of the estimation of the time elapsed since the overdose. R. B. PAYNE St James’s University Hospital, P. SHERIDAN Leeds LS9 7TF
CYSTEAMINE INJECTION FOR PARACETAMOL POISONING
SIR,-Cysteamine, a drug not yet generally available, is used with success in patients severely poisoned with paracetamol (acetaminophen). However, stability of solutions of cystea2 mme has been a problem. 1 Injections of cysteamine hydrochloride have been prepared either as a freeze-dried product to be reconstituted in 5% dextrose immediately before use,3 or as freshly prepared solutions to be injected directly through a disposable Millipore filter attached to a syringe.4 The preparation of freeze-dried cysteamine for injection is time consuming and requires special equipment in the hospital pharmacy. Bacterial contamination after direct Millipore filtration is a real danger. We investigated samples of six commercially available cysteamine hydrochloride preparations.5 One of these substances had deteriorated to the extent of containing about 40% as the oxidation product, cystamine. A freeze-dried preparation for injection had deteriorated by about 20%. A stable injection can be prepared as follows. Cysteamine hydrochloride of a good quality is dissolved in ascorbic acid solution 11.5 mmol/1; after filtration the solution is filled into suitable vials or ampoules under nitrogen. The solution is sterilised by autoclaving in saturated steam at 1150C for 30 min. A stable ready-to-hand injection is then available.
displayed without adding VAR, and 4.2000 is the corwhen using the check figures. Other simple check figures give correct answers also. Omitting two ENT therefore shortens the program to 11 steps. There are likely to be alternative ways of programming several of the equations but certainly the shorter ways are preis in fact
rect answer
ferable. Department of Anæsthesia, Janeway Child Health Centre, St. John’s, Newfoundland A1A 1R8,
D. G. Ross
Canada
EFFECT OF ANTACIDS ON ABSORPTION OF CIMETIDINE
SiR,—The histamine H2-receptor antagonist, cimetidine, is effective treatment for peptic ulceration.’-’ Patients treated with cimetidine may also take antacids to relieve pain during the early period of treatment. Since some antacids, especially an
those containing aluminium hydroxide, may act as adsorbents and interact with drugs in the gastrointestinal tract to alter their absorption, we studied the absorption of cimetidine when it was administered alone or with an antacid. The study was done in six healthy subjects (two females, four males) aged 22-42 years. Each was studied on three occaBLOOD CONCENTRATIONS CIMETIDINE
(jg/mt):
MEAN:i:S.E.M.
Hospital Pharmacy, Regional Protestant Hospital,
J. R. B. J. BROUWERS
Bennekom, Netherlands
Hospital Pharmacy, Andreas Hospital, P.
Amsterdam
VERMEIJ
PROGRAMMABLE CALCULATORS
studied,
S)R,—I read with enthusiasm Dr Ross and Dr Manson’s article (Aug. 28, p. 446) since I own a ’Sinclair Scientific ProWhen I checked the alveolar air equawith the variables provided I consistently got the answer B=4.8333 instead of x=4.2000 suggested. The program printed contains an error. All programs should end with ... B tR:_cct otherwise the results of the final calculation will not
grammable’ calculator. tion
be
displayed.
The program could be reduced by two unnecessary ENT entries to read BE/STO/ENT/VAR/-/VAR/—/VAR/X/-/RCL/+/
KAr_E((12 steps). St Thomas’s House, St T homas’s Hospital Medical London SE1
School,
*/This letter has been shown
J. H. WEST to
Dr
Ross, whose reply fol-
lows.—ED. L.
SIR,-Mr West is quite correct in pointing out that the second and third ENT are unnecessary, but the final calculation
1 Prescott, L F, Newton, R. W., Swainson, C. P., A R W, Matthew, H. Lancet, 2 Heyst, v., A. N. P, Douze, J. M.
Wright N , Forrest, 1974, i, 588. C., Pikaar, S. A. Ned. T Geneesk. 1976,
120, 1151 3 Prescott, D. F, Park, J., Sutherland, G. R., Smith, I. J., Proudfoot, Lancet, 1976, ii, 109. 4 Douglas, P, A Hamlyn, A. N., James, O. ibid 1976, i, 111. 5 Brouwers, J R B. J , Vermeij, P. Pharm.Wkbl. 1976, 111, 204.
sions not less than 1 week apart. On one occasion, cimetidine 400 mg was taken alone with a breakfast consisting of orange juice, cereal, toast and marmalade, and coffee; this was repeated on the other two occasions but antacid was also taken at 6 P.M. and 10 P.M. on the previous evening, at 8.15 A.M. breakfast, and 30, 90, and 150 m after cimetidine. Two antacids were one was ’Rennie’ (2 tablets/dose) which is the antacid being used in many of the controlled clinical trials of cimetidine, the other was ’Aludrox SA’ (20 ml dose) containing aluminium hydroxide gel 4.75 ml and magnesium hydroxide 100 mg in each 5 ml. The order of treatment was randomised. Venous blood-samples were collected every 15 or 30 min for 4 h after dosing, and urine was collected for 24 h. Blood and urine cimetidine concentrations were estimated by high-pressure liquid chromatography. Blood data were analysed by Student’st test. The mean blood concentrations for five of the eleven times are shown in the table. No statistically significant difference in blood concentration of cimetidine was demonstrated between dosage regimens. There were no significant differences in urinary output of cimetidine between any of the regimens. The blood and urine concentrations of cimetidine obtained in this study indicate that the concurrent administration of cimetidine and antacids in the form of rennie and aludrox causes no alteration in the absorption and excretion of cimetidine. Rennie tablets
were
provided by Nicholas Laboratories Ltd.
Research Institute, Smith Klme & French Laboratories Ltd, Welwyn Garden City, Herts
H , Stekelman, M., Milton-Thompson, G. J., MisJ Lancet, 1976, i, 337 2. Haggie, S. J , Fermont, D C., Wyllie, J. H. ibid p. 983. 3. Blackwood, W S , Maudgal, D P., Pickard, R. G., Lawrence, D , North-
1.
Pounder,
R. S , Hunt, R.
iewicz, J
A. T
W. L. BURLAND D. W. DARKIN M. W. MILLS
field, T C ibid 1976, ii, 174 G., Walan, A ibid. p. 161.
4. Bodemar,