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PHENYTOIN DOSAGE
278 state that the importance of sympathetic activity in digitalisinduced arrhythmias is not very obvious, and we feel that the autonomic nervous system is an important target for antiarrhythmic intervention. Division of Cardiology and Clinical Pharmacology, Department of Medicine, New York Medical College, New York, N.Y., and Department of Pharmacology
EFFECT OF CHANGE IN PHENYTOIN DOSAGE ON PLASMA LEVEL
N. CAGIN J. SOMBERG
J. KLEID R. GILLIS B. LEVITT.
Georgetown University, Washington, D.C.
.
SI UNITS
SIR,-At meeting of the’ Brighton District Medical Advisory Committee the directive from the Department of Health and Social Security regarding the procedure for initiating the use of SI units in the National Health Service was presented. During the discussion it became apparent that, although no direct advantage in the clinical care of the patient could be claimed for the new system, many disadvantages and dangers could be cited. Also, at a time of great financial stringency, a new system of measurement, with its attendant costs and inconvenience, was being forced upon clinicians without their opinions having been sought in any depth, if at all. It was resolved therefore that " this committee feels that it would be inappropriate to initiate the use of SI units in the hospitals of the Brighton district at this time and the District Management Team be informed accordingly ". The matter was further discussed at the District Hospitals Medical Committee when the resolution outlined above a
was
recent
unanimously supported.
Brighton General Hospital; Brighton BN2 3EW.
AUSTIN BROWN, Chairman, Brighton District Hospitals Medical Advisory Committee, and Brighton District Hospitals
We recently completed a bioavailability study involving 60 patients1 at the end of which 20 required adjustment of the dosage. This was done, and the patients were monitored five months later. In this inpatient population, drug administration is carefully monitored and compliance are few. In addition there were no significant alterations in weight, clinical state, or administration of other drugs over the period. Two estimations were madeone week apart-at each end of the period, and the mean levels compared. The results are set out in the accompanying table, which shows that the changes in steady-state plasma levels achieved following an alteration of 50 mg. a day can mean a transition from a subtherapeutic to a toxic level or vice versa. A nomogram produced by Richens and Dunlop (see p. 247) also shows that, in order to obtain a satisfactory plasma phenytoin level in some patients, alterations in the daily dose of less than 50 mg. are required. Is it not time that those who carry the responsibility for treating epileptics started pressing the manufacturers for tablets containing 25 mg. or less and thus make possible much finer ccntrol ?
problems
Department of Biochemical Medicine, Ninewells Hospital and Medical School, Dundee DD2 1UD.
M. J. STEWART.
Medical Committee.
PRESERVING THE mm Hg SIR,-When one reads the height of a column of mercury, it is sensible to record the results in mm Hg. After 75 years of use, the Riva-Rocci sphygmanometer remains the most convenient and reliable method of measuring bloodpressure in clinical practice, and until someone designs a better instrument it seems absurd to record blood-pressures in the new international units (July 19, p. 135). By contrast, Van Slyke apparatuses now collect dust in laboratory cupboards, and as the new methods of blood-gas analysis do not involve the use of mercury there’are advantages in recording results in the SI unit of pressure, the pascal. One advantage is that it helps us to remember Pascal (1623-62), who was one of the world’s truly Great Men. All medical students, young or old, would profit from studying his simple and elegant experiments, which showed that air had weight, and from reading his literary and religious works. Of those, Pensées is easily obtainable in translation as a Penguin classic. Department of Physiology, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG.
inaiviauai vames.
R. PASSMORE.
PHENYTOIN DOSAGE SIR,-Attempts to obtain steady-state plasma levels within the therapeutic range in patients receiving phenytoin are complicated by the problems of patient non-compliance, differences in bioavailability between preparations, and difficulties related to analysis and collection of specimens.
SERUM-AMINOACIDS AND BRAIN TRYPTOPHAN UPTAKE SIR,-Professor Daniel and his co-workerssuggested that competition by other large neutral aminoacids may be of little importance in regulating brain tryptophan uptake. Their conclusion was based on observations of the increases in the concentrations of these aminoacids required to reduce tryptophan uptake by 50%, and disagrees with the conclusions of two other groups of workers.34 During studies on the effects of chlorpromazine on brain serotonin metabolism, I observed changes in brain tryptophan uptake and serotonin synthesis correlated with changes in serum diffusible tryptophan and reduction in serum totalaminoacid concentrations without change in diffusible tryptophan. Rats were used in these experiments; control animals were injected with 0-15M sodium chloride, and experimental animals were injected with a solution of chlorpromazine (’ Largactil’, May and Baker) at a dose of lOmg/kg body-weight. One group of animals received a single dose of the drug 4 hours before killing, and the other repeated administration daily for 11 days. Serum total and diffusible tryptophan, serum-total-aminoacids and brain serotonin and tryptophan concentrations were determined. The accumulation of radioactive tryptophan and serotonin in the brain was assessed following injection 1. 2.
3. 4.
Stewart, M. J., Ballinger, B. R., Devlin, E. J., Miller, A. Y., Ramsay, A. C. Eur. J. clin. Pharmac. (in the press). Daniel, P. M., Love, E. R., Moorhouse, S. R., Pratt, O. E. Lancet, July 26, 1975, p. 179. Curzon, G., Knott, P. J., Murray-Lyon, I. M., Record, C. O., Williams, R. ibid. 1975, i, 1092. Munro, H. N., Fernstrom, J. D., Wurtman, R. J. ibid. p. 722.
EFFECT OF CHANGE IN PHENYTOIN DOSAGE ON PLASMA LEVEL
N. CAGIN J. SOMBERG
J. KLEID R. GILLIS B. LEVITT.
Georgetown University, Washington, D.C.
.
SI UNITS
SIR,-At meeting of the’ Brighton District Medical Advisory Committee the directive from the Department of Health and Social Security regarding the procedure for initiating the use of SI units in the National Health Service was presented. During the discussion it became apparent that, although no direct advantage in the clinical care of the patient could be claimed for the new system, many disadvantages and dangers could be cited. Also, at a time of great financial stringency, a new system of measurement, with its attendant costs and inconvenience, was being forced upon clinicians without their opinions having been sought in any depth, if at all. It was resolved therefore that " this committee feels that it would be inappropriate to initiate the use of SI units in the hospitals of the Brighton district at this time and the District Management Team be informed accordingly ". The matter was further discussed at the District Hospitals Medical Committee when the resolution outlined above a
was
recent
unanimously supported.
Brighton General Hospital; Brighton BN2 3EW.
AUSTIN BROWN, Chairman, Brighton District Hospitals Medical Advisory Committee, and Brighton District Hospitals
We recently completed a bioavailability study involving 60 patients1 at the end of which 20 required adjustment of the dosage. This was done, and the patients were monitored five months later. In this inpatient population, drug administration is carefully monitored and compliance are few. In addition there were no significant alterations in weight, clinical state, or administration of other drugs over the period. Two estimations were madeone week apart-at each end of the period, and the mean levels compared. The results are set out in the accompanying table, which shows that the changes in steady-state plasma levels achieved following an alteration of 50 mg. a day can mean a transition from a subtherapeutic to a toxic level or vice versa. A nomogram produced by Richens and Dunlop (see p. 247) also shows that, in order to obtain a satisfactory plasma phenytoin level in some patients, alterations in the daily dose of less than 50 mg. are required. Is it not time that those who carry the responsibility for treating epileptics started pressing the manufacturers for tablets containing 25 mg. or less and thus make possible much finer ccntrol ?
problems
Department of Biochemical Medicine, Ninewells Hospital and Medical School, Dundee DD2 1UD.
M. J. STEWART.
Medical Committee.
PRESERVING THE mm Hg SIR,-When one reads the height of a column of mercury, it is sensible to record the results in mm Hg. After 75 years of use, the Riva-Rocci sphygmanometer remains the most convenient and reliable method of measuring bloodpressure in clinical practice, and until someone designs a better instrument it seems absurd to record blood-pressures in the new international units (July 19, p. 135). By contrast, Van Slyke apparatuses now collect dust in laboratory cupboards, and as the new methods of blood-gas analysis do not involve the use of mercury there’are advantages in recording results in the SI unit of pressure, the pascal. One advantage is that it helps us to remember Pascal (1623-62), who was one of the world’s truly Great Men. All medical students, young or old, would profit from studying his simple and elegant experiments, which showed that air had weight, and from reading his literary and religious works. Of those, Pensées is easily obtainable in translation as a Penguin classic. Department of Physiology, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG.
inaiviauai vames.
R. PASSMORE.
PHENYTOIN DOSAGE SIR,-Attempts to obtain steady-state plasma levels within the therapeutic range in patients receiving phenytoin are complicated by the problems of patient non-compliance, differences in bioavailability between preparations, and difficulties related to analysis and collection of specimens.
SERUM-AMINOACIDS AND BRAIN TRYPTOPHAN UPTAKE SIR,-Professor Daniel and his co-workerssuggested that competition by other large neutral aminoacids may be of little importance in regulating brain tryptophan uptake. Their conclusion was based on observations of the increases in the concentrations of these aminoacids required to reduce tryptophan uptake by 50%, and disagrees with the conclusions of two other groups of workers.34 During studies on the effects of chlorpromazine on brain serotonin metabolism, I observed changes in brain tryptophan uptake and serotonin synthesis correlated with changes in serum diffusible tryptophan and reduction in serum totalaminoacid concentrations without change in diffusible tryptophan. Rats were used in these experiments; control animals were injected with 0-15M sodium chloride, and experimental animals were injected with a solution of chlorpromazine (’ Largactil’, May and Baker) at a dose of lOmg/kg body-weight. One group of animals received a single dose of the drug 4 hours before killing, and the other repeated administration daily for 11 days. Serum total and diffusible tryptophan, serum-total-aminoacids and brain serotonin and tryptophan concentrations were determined. The accumulation of radioactive tryptophan and serotonin in the brain was assessed following injection 1. 2.
3. 4.
Stewart, M. J., Ballinger, B. R., Devlin, E. J., Miller, A. Y., Ramsay, A. C. Eur. J. clin. Pharmac. (in the press). Daniel, P. M., Love, E. R., Moorhouse, S. R., Pratt, O. E. Lancet, July 26, 1975, p. 179. Curzon, G., Knott, P. J., Murray-Lyon, I. M., Record, C. O., Williams, R. ibid. 1975, i, 1092. Munro, H. N., Fernstrom, J. D., Wurtman, R. J. ibid. p. 722.