656 blasts in the bone-marrow, resistance to the usual leukaemia therapy, prolonged survival without treatment despite morphological evidence of active disease, and normal plateletcounts.
Further observations will be required to determine the frequency, possible cell specificity, and diagnostic, prognostic, and therapeutic implications of this morphological finding. We thank Wendie Smith and
James
S. Godron for the
photomicro-
graphs. Division of
Hematopathology,
Department of Laboratory Medicine,
and
H. R. SCHUMACHER E. PERLIN W. M. MILLER S. A. STASS
Division of Hematology-Oncology, Department of Medicine, National Naval Medical Center, Bethesda, Maryland 20014, U.S.A.
Salivary phenytoin levels DRUG FORMULATION AND SALIVARY PHENYTOIN
O=serum level in
MEASUREMENTS
X=carbamazepine
with previous workers we have found receiving phenytoin, with or without other epileptics drugs, salivary concentrations are about 10% of those found in plasma or serum.’-4 However, one of our patients had serum
SIR,-In
common
mal. To find
lations
out how long phenytoin from different drug formumight remain in the mouth and interfere with salivary
SALIVARY PHENYTOIN CONCENTRATIONS
(µg/ml) AFTER 50 mg OF
PHENYTOIN IN DIFFERENT FORMULATIONS BY VOLUNTEERS
A, B,
AND C
one
patient.
g/mt. 100 mg,
phenytoin 150
mg, and
valproate
100
mg.
Y=valproate
that in
concentration of 9 fLglml and a saliva concentration of 12 fLglml; samples had been taken 1 th after the dose. The phenytoin prescribed was in the form of ’Infatabs’ (Parke-Davis), a tablet which is chewed rather than swallowed. Before this patient’s morning medication the saliva/plasma ratio was nor-
in
100 mg.
before medication. The coefficient of variation throughout the day in this patient was 5.3% with coefficient of variation of the analytical technique at this level being 4%. Measurements of anticonvulsant drugs in saliva are much easier in many epileptic patients, and permit more detailed studies without inconvenience to the patients. Account must be taken of the fonnulation of the drug, and care should be taken to remove any remaining drug before sampling within 3-5 h of the dose if syrup or chewable forms are prescribed. Department of Clinical Biochemistry, St Albans City Hospital,
GWENDOLEN J. AYERS DAVID BURNETT
St Albans, Herts AL3 5PN
SALIVARY CARBAMAZEPINE CONCENTRATIONS
SIR,-It has been suggested that anticonvulsant therapy with phenytoin could be more appropriately monitored by sali1 vary, rather than plasma drug concentrations. 1 1.
Reynolds, F., Ziroyanis,
P.
N., Jones,
N.
F., Smith, S. E., Lancet, 1976, ii,
384. 2.
Schmidt, D.
ibid.
p. 639.
volunteers were given 50 mg equivalents of ’Epanutin’ suspension (10 ml), infatabs, and ordinary tablets (Boots). Since children occasionally chew tablets one volunteer measurements
chewed a tablet. Saliva was collected from the volunteers before medication and afterwards (see table). Our normal technique is to stimulate salivary flow by asking the patient to chew parafilm, but in this study no stimulation was used to avoid possible removal of drug by parafilm. When a tablet of 50 mg was taken by two volunteers who had not previously received phenytoin, none was detected in saliva in a 7 h period. However, with syrup (table) phenytoin was still detected at 2 h and with infatabs and chewed tablets substantial amounts were present at 3 h. Clearly if satisfactory measurements are to be made using saliva then the samples should be collected before the morning medication. The figure shows salivary determinations of phenytoin on a patient throughout the day, the first sample being collected Bochner, F., Hooper, W. D., Sutherland, J. M., Eadie, M. J., Tyrer, J. H. Archs Neurol. 1974, 31, 57. 2. Schmidt, D., Kuperferberg, H. J. Epilepsia, 1975, 16, 735. 3. Troupin, A. S., Friel, P. ibid. p. 223. 4. Cook, C. E., Amerson, E., Poole, W. K., Lesser, P., O’Thama, L. Clin. Pharmac. Ther. 1975, 18, 742. 1.
Plasma concentration of Correlation between in five volunteers.
Carbamazepine pmolll
carbamazepine levels in plasma and saliva
657 We have measured the salivary concentrations of carbamazepine after single oral doses in five healthy volunteers using gas-chromatography. The drug is separated on a column ofto5%a ’Apiezon L’ 1% KOH on ’Diatomite CLQ’ connected nitrogen detector. Mixed saliva samples were obtained by mechanical stimulation. The concentration in these samples at 3, 5, 8, 24, 28, 32, 48, 96, and 120 h after taking the dose orally was 31± 0.7%
(mean±s.D., n=36) of the corresponding plasma
concentra-
tion. Throughout the range measured the concentrations in saliva and plasma showed excellent agreement (see figure). Although carbamazepine is bound to plasma protein, there was close correlation (r=0.95, r