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NOMOGRAM FOR KANAMYCIN DOSAGE
45 In view of these findings we would recommend that thyroid function be evaluated before lithium is started and at regular intervals during treatment. The possibility of lithium-induced hypothyroidism presenting a similar clinical picture to a depressive relapse should be borne in
mind. Leverndale Hospital, Glasgow G53 7TU.
E. H. BENNIE.
Department of Medicine, Western Infirmary, Glasgow G11 6NT.
J.
H. LAZARUS.
NOMOGRAM FOR KANAMYCIN DOSAGE SIR,-A simple method for determining dosage schedules of kanamycin has been developed. The method is applicable to patients with all degrees of renal impairment from normal function to severe oliguria and anuria. The computer program described earlierhas been used to construct the nomogram shown in the accompanying figure. A suitable dose schedule may be obtained for an individual patient provided that the serum-creatinine
patients with renal insufficiency it is probably still desirable to check the serum concentrations by bioassay once or twice during a course of treatment. If the patient is severely oliguric the dose schedule should be obtained by joining with a straight line the lowest point on line C to the body-weight on scale D. After a period of hasmodialysis of 6 hours or more a booster dose of half the loading dose is necessary in addition to the maintenance dose indicated by the nomogram. We have found it satisfactory to give the booster dose intravenously over a period of 10 minutes during washback at the end of dialysis. It is necessary to redetermine the dose schedule at intervals in a patient with a changing serum concentration of creatinine due to alteration in renal function. The nomogram dose schedules are simple to implement. The doses are all given in exact multiples of 125 mg. (0-5 ml. of a solution containing 500 mg. in 2 ml.) and the intervals between doses are all given in exact multiples of 12 hours. Department of Pharmacology, University of Manchester, Manchester M13 9PT.
G. E. MAWER S. B. LUCAS.
Department of Maths and Computer Studies, Harris College, Preston PR1 2TQ.
J. G. MCGOUGH.
L-DOPA AND PYRIDOXINE SIR,-I have read the letters of Dr. Evered1 and Dr. Johnston2 on L-dopa and pyridoxine with great interest.
Although Dr. Evered’s important hypothesis suggested that a chemical reaction between L-dopa and pyridoxal 5’phosphate might explain the clinically3 and experimentally4 observed antagonism between L-dopa and pyridoxine, the role of the tetrahydroisoquinolines possibly formed is still
(mg. per 100 ml.), the age (years), body-weight (kg.) are known. The nomogram is operated as follows: concentration
and the
1. Join with a straight line the serum-creatinine concentration appropriate to the sex on scale A and the age on scale B. Mark the point at which the straight line cuts line C. 2. Join with a straight line the mark on line C and the bodyweight on scale D. Mark the points at which this line cuts the dosage lines L and M. 3. The loading dose (mg.) is written against the marked part of line L. The maintenance dose (mg.) and the appropriate interval (hours) between doses are written against the marked
part of line M.
The nomogram is designed to give serum concentrations kanamycin within the commonly accepted therapeutic range (10-30 g. per ml.) 2 hours after each dose. In
of
1.
G. E., Knowles, B. R., Lucas, S. B., Stirland, R. M., Tooth, J. A. Lancet, 1972, i, 12.
Mawer,
unknown. The formation of L-dopa/pyridoxal-5’-phosphate complexes has been demonstrated by Clark et al.,6 Evered,1 and Fellman and Roth.6 Using radioisotope techniques, Dr. Vogeland we 8-10 have found that large doses of pyridoxal 5’-phosphate inhibited both a nonenzymatic and enzymatic oxidation of dopa. The results obtained suggested that large doses of L-dopa and pyridoxine given to patients with Parkinson’s disease might enhance the formation of L-dopa-pyridoxal 5’-phosphate complexes in the human body, which in turn could inhibit dopa-decarboxylase activity.8-10 Perhaps a fall in dopamine production due to the inhibition of dopa decarboxylation by pyridoxal 5’-phosphate may explain the antagonism of the activity of L-dopa by pyridoxine in the treatment of parkinsonism. Also, this may explain the role of pyridoxine in the production of many beneficial effects 3,11,12 as well as side-effects 3,11 of L-dopa. A fall in plasma-L-dopa levels and in urinary excretion of L-dopa and dopamine was found in patients with parkinsonism who received both L-dopa and pyridoxine; unfortunately, no method is known 1. 2. 3.
Evered, D. F. Lancet, 1971, i, 914. Johnston, G. A. R. ibid. 1971, ii, 220. Boudin, G., Castaigne, P., Lhermitte, F., Beck, H., Guillard, A., Marteau, P., Pepin, B., Rondot, P., Raphy, B. Rev. neurol. 1970, 122, 80.
4. Lechat, P., Streichenberger, G., Boismare, F., Letteron, N. J. Pharmac. 1970, 1, 525. 5. Clark, C. T., Weissback, H., Udenfriend, S. J. biol. Chem. 1954, 210, 139. 6. Fellman, J. H., Roth, E. S. Biochemistry, 1971, 10, 408. 7. Vogel, W. H. Naturwissenschaften, 1969, 56, 462. 8. Tran, N., Laplante, M. Int. J. Biochem. (in the press). 9. Tran, N. J. nucl. Med. 1972, 13, 349. 10. Tran, N. Un. med. Can. 1972, 101, 746. 11. Jameson, H. D. J. Am. med. Ass. 1970, 211, 1700. 12. Leon, A. S., Spiegel, H. E., Thomas, G., Abrams, W. B. ibid.
1971, 218, 1924.
mind. Leverndale Hospital, Glasgow G53 7TU.
E. H. BENNIE.
Department of Medicine, Western Infirmary, Glasgow G11 6NT.
J.
H. LAZARUS.
NOMOGRAM FOR KANAMYCIN DOSAGE SIR,-A simple method for determining dosage schedules of kanamycin has been developed. The method is applicable to patients with all degrees of renal impairment from normal function to severe oliguria and anuria. The computer program described earlierhas been used to construct the nomogram shown in the accompanying figure. A suitable dose schedule may be obtained for an individual patient provided that the serum-creatinine
patients with renal insufficiency it is probably still desirable to check the serum concentrations by bioassay once or twice during a course of treatment. If the patient is severely oliguric the dose schedule should be obtained by joining with a straight line the lowest point on line C to the body-weight on scale D. After a period of hasmodialysis of 6 hours or more a booster dose of half the loading dose is necessary in addition to the maintenance dose indicated by the nomogram. We have found it satisfactory to give the booster dose intravenously over a period of 10 minutes during washback at the end of dialysis. It is necessary to redetermine the dose schedule at intervals in a patient with a changing serum concentration of creatinine due to alteration in renal function. The nomogram dose schedules are simple to implement. The doses are all given in exact multiples of 125 mg. (0-5 ml. of a solution containing 500 mg. in 2 ml.) and the intervals between doses are all given in exact multiples of 12 hours. Department of Pharmacology, University of Manchester, Manchester M13 9PT.
G. E. MAWER S. B. LUCAS.
Department of Maths and Computer Studies, Harris College, Preston PR1 2TQ.
J. G. MCGOUGH.
L-DOPA AND PYRIDOXINE SIR,-I have read the letters of Dr. Evered1 and Dr. Johnston2 on L-dopa and pyridoxine with great interest.
Although Dr. Evered’s important hypothesis suggested that a chemical reaction between L-dopa and pyridoxal 5’phosphate might explain the clinically3 and experimentally4 observed antagonism between L-dopa and pyridoxine, the role of the tetrahydroisoquinolines possibly formed is still
(mg. per 100 ml.), the age (years), body-weight (kg.) are known. The nomogram is operated as follows: concentration
and the
1. Join with a straight line the serum-creatinine concentration appropriate to the sex on scale A and the age on scale B. Mark the point at which the straight line cuts line C. 2. Join with a straight line the mark on line C and the bodyweight on scale D. Mark the points at which this line cuts the dosage lines L and M. 3. The loading dose (mg.) is written against the marked part of line L. The maintenance dose (mg.) and the appropriate interval (hours) between doses are written against the marked
part of line M.
The nomogram is designed to give serum concentrations kanamycin within the commonly accepted therapeutic range (10-30 g. per ml.) 2 hours after each dose. In
of
1.
G. E., Knowles, B. R., Lucas, S. B., Stirland, R. M., Tooth, J. A. Lancet, 1972, i, 12.
Mawer,
unknown. The formation of L-dopa/pyridoxal-5’-phosphate complexes has been demonstrated by Clark et al.,6 Evered,1 and Fellman and Roth.6 Using radioisotope techniques, Dr. Vogeland we 8-10 have found that large doses of pyridoxal 5’-phosphate inhibited both a nonenzymatic and enzymatic oxidation of dopa. The results obtained suggested that large doses of L-dopa and pyridoxine given to patients with Parkinson’s disease might enhance the formation of L-dopa-pyridoxal 5’-phosphate complexes in the human body, which in turn could inhibit dopa-decarboxylase activity.8-10 Perhaps a fall in dopamine production due to the inhibition of dopa decarboxylation by pyridoxal 5’-phosphate may explain the antagonism of the activity of L-dopa by pyridoxine in the treatment of parkinsonism. Also, this may explain the role of pyridoxine in the production of many beneficial effects 3,11,12 as well as side-effects 3,11 of L-dopa. A fall in plasma-L-dopa levels and in urinary excretion of L-dopa and dopamine was found in patients with parkinsonism who received both L-dopa and pyridoxine; unfortunately, no method is known 1. 2. 3.
Evered, D. F. Lancet, 1971, i, 914. Johnston, G. A. R. ibid. 1971, ii, 220. Boudin, G., Castaigne, P., Lhermitte, F., Beck, H., Guillard, A., Marteau, P., Pepin, B., Rondot, P., Raphy, B. Rev. neurol. 1970, 122, 80.
4. Lechat, P., Streichenberger, G., Boismare, F., Letteron, N. J. Pharmac. 1970, 1, 525. 5. Clark, C. T., Weissback, H., Udenfriend, S. J. biol. Chem. 1954, 210, 139. 6. Fellman, J. H., Roth, E. S. Biochemistry, 1971, 10, 408. 7. Vogel, W. H. Naturwissenschaften, 1969, 56, 462. 8. Tran, N., Laplante, M. Int. J. Biochem. (in the press). 9. Tran, N. J. nucl. Med. 1972, 13, 349. 10. Tran, N. Un. med. Can. 1972, 101, 746. 11. Jameson, H. D. J. Am. med. Ass. 1970, 211, 1700. 12. Leon, A. S., Spiegel, H. E., Thomas, G., Abrams, W. B. ibid.
1971, 218, 1924.