Br. J. clin. Pharmac. (1979), 8
LETTERS TO THE EDITORS
9
J.W. PAXTON & SUE FOOTE
8
Department of Pharmacology & Clinical Pharmacology, University of Auckland, School of Medicine, Auckland, New Zealand
7 0
E
509
6
Received June 5, 1979
5 I 0-
o
4
References
3
CHIOU, W.L., CHANG, K. & PENG, G.W. (1976). Precaution in the monitoring of drug levels in saliva. Abnormal salicylate levels after oral dosing. J. clin. Pharmac., 16, 158-160.
(I)
COOK, C.E., AMERSON, E., POOLE, W.K., LESSER, P. &
2~~~~~~~~
2
1
O'TUAMA, L. (1976). Phenytoin and Phenobarbital concentrations in saliva and plasma measured by radioimmunoassay. Clin. Pharmac. Ther., 18, 742-747.
3
Time (h)
Figure 2 Salivary DPH concentrations in subject A after retaining in the mouth for 45s 2xlOOmg capsules (0) and 2xlOOmg tablets (O) and in subject B, 2xlOOmg capsules for 30s (0) and 2 x 100 mg tablets for 45 s (E), and in subjects A (A) and B (A) after two mouth washes with water. Each point is the mean of duplicate analyses.
their mouths with two washes of water. In the subsequent saliva specimens no concentrations greater than 0.1 gmol/1 were detected. These results indicate that after oral dosing with both tablets and capsules of DPH a significant residue of drug may be left in the mouth which can contaminate the subsequent whole saliva specimens collected up to 3 h after administration. This problem may be eliminated by thorough cleansing of the mouth with water. We would recommend this procedure if whole saliva samples are to be obtained for DPH measurement during the 3 h period after administration of either capsules or tablets. This work was supported by grants from the M.R.C. (N.Z.) and from the National Children's Health Research Foundation (N.Z.).
NOWLIN, J., M.G., BROWN, L., HORNING, LERTRATANANGKOON, K., KELLAWAY, P. & ZION,
T.E. (1977). Use of saliva in therapeutic drug monitoring. Clin. Chem., 23, 157-164. JOUBERT, P.H., MOLLER, F.O. & AUCAMP, B.N. (1976). Salivary digoxin concentrations. Br. J. clin. Pharmac., 3, 673-674. McAULIFFE, J.J., SHERWIN, A.L., LEPPIK, I.E., FAYLE, S.A.
& PIPPENGER, C.E. (1977). Salivary levels of anticonvulsants: A practical approach to drug monitoring. Neurology, 27, 409-413. MUCKLOW, J.C., BENDING, M.R., KAHN, G.C. & DOLLERY, T. (1978). Drug concentration in saliva. Clin.
Pharmac. Ther., 24, 563-570. PAXTON, J.W., ROWELL, FJ., RATCLIFFE, J.G., LAMBIE, D.G., NANDA, R., MELVILLE, I.D. & JOHNSON, R..
(1977). Salivary phenytoin radioimmunoassay: A simple method for the assessment of non-protein bound drug concentrations. Eur. J. clin. Pharmac., 11, 71-74. PAXTON, J.W., WHITING, B. & STEPHEN, K.W. (1977). Phenytoin concentrations in mixed, parotid and submandibular saliva and serum measured by radioimmunoassay. Br. J. clin. Pharmac., 4, 185-191. REYNOLDS, F., ZIROYANIS, P.N., JONES, N.F. & SMITH,
S.E. (1976). Salivary phenytoin concentrations in epilepsy and in chronic renal failure. Lancet, ii, 384-386. WADA, J.A., TROUPIN, A.S., FRIEL, P., REMICK, R., LEAL,
K. & PEARMAIN, J. (1978). Pharmacokinetic comparison of tablet and suspension dosage forms of carbamazepine. Epilepsia, 19, 251-255.
PHENYTOIN ABSORPTION IN PATIENTS WITH ILEOJEJUNAL BYPASS We read with interest the paper by Kennedy & Wade (1979) on phenytoin absorption in patients with ileojejunal bypass. In the discussion the authors express their
astonishment at finding a significantly shorter halflife of elimination in the bypass patients compared with the control group. Recalculation of the difference between the two means using the values
510
LETTERS TO THE EDITORS
Br. J.
supplied in the paper, gave a t value of 1.32 which at 14 degrees of freedom corresponds to a P value of 0.3-0.2. This should save the authors any speculation about the cause of a non-existent difference. R.E. SCHNEIDER & H. BISHOP Department of Therapeutics and Clinical Pharmacology, The Medical School, Edgbaston, Birmingham BI5 2TJ
clin. Pharmac. (1979), 8 Received June 11, 1979
Reference KENNEDY, M.C. & WADE, D.N. (1979). Phenytoin absorption in patients with ileojejunal bypass. Br. J. clin. Pharmac., 7, 515-518.
PHENYTOIN ABSORPTION IN PATIENTS WITH ILEOJEJUNAL PYPASS Thank you for pointing out an error in the calculated P value presented in the results of this paper (Kennedy & Wade, 1979). The significance calculated by one tail t-test with 14 degrees of freedom is, in fact, 0.10263. However, the conclusions shown in the Discussion appear to be sound. 'However, the difference was smail and a larger number of patients would be needed to be certain this difference was real.' Nowhere in the Discussion do the authors express 'astonishment' or even mild surprise.
D.N. WADE Department of Clinical Pharmacology, St Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia
Received August 13, 1979
Reference KENNEDY, M.C. & WADE, D.N. (1979). Phenytoin absorption in patients with ileojejunal bypass. Br. J. clin.
Pharmac., 7, 515-518.
LETTERS TO THE EDITORS
9
J.W. PAXTON & SUE FOOTE
8
Department of Pharmacology & Clinical Pharmacology, University of Auckland, School of Medicine, Auckland, New Zealand
7 0
E
509
6
Received June 5, 1979
5 I 0-
o
4
References
3
CHIOU, W.L., CHANG, K. & PENG, G.W. (1976). Precaution in the monitoring of drug levels in saliva. Abnormal salicylate levels after oral dosing. J. clin. Pharmac., 16, 158-160.
(I)
COOK, C.E., AMERSON, E., POOLE, W.K., LESSER, P. &
2~~~~~~~~
2
1
O'TUAMA, L. (1976). Phenytoin and Phenobarbital concentrations in saliva and plasma measured by radioimmunoassay. Clin. Pharmac. Ther., 18, 742-747.
3
Time (h)
Figure 2 Salivary DPH concentrations in subject A after retaining in the mouth for 45s 2xlOOmg capsules (0) and 2xlOOmg tablets (O) and in subject B, 2xlOOmg capsules for 30s (0) and 2 x 100 mg tablets for 45 s (E), and in subjects A (A) and B (A) after two mouth washes with water. Each point is the mean of duplicate analyses.
their mouths with two washes of water. In the subsequent saliva specimens no concentrations greater than 0.1 gmol/1 were detected. These results indicate that after oral dosing with both tablets and capsules of DPH a significant residue of drug may be left in the mouth which can contaminate the subsequent whole saliva specimens collected up to 3 h after administration. This problem may be eliminated by thorough cleansing of the mouth with water. We would recommend this procedure if whole saliva samples are to be obtained for DPH measurement during the 3 h period after administration of either capsules or tablets. This work was supported by grants from the M.R.C. (N.Z.) and from the National Children's Health Research Foundation (N.Z.).
NOWLIN, J., M.G., BROWN, L., HORNING, LERTRATANANGKOON, K., KELLAWAY, P. & ZION,
T.E. (1977). Use of saliva in therapeutic drug monitoring. Clin. Chem., 23, 157-164. JOUBERT, P.H., MOLLER, F.O. & AUCAMP, B.N. (1976). Salivary digoxin concentrations. Br. J. clin. Pharmac., 3, 673-674. McAULIFFE, J.J., SHERWIN, A.L., LEPPIK, I.E., FAYLE, S.A.
& PIPPENGER, C.E. (1977). Salivary levels of anticonvulsants: A practical approach to drug monitoring. Neurology, 27, 409-413. MUCKLOW, J.C., BENDING, M.R., KAHN, G.C. & DOLLERY, T. (1978). Drug concentration in saliva. Clin.
Pharmac. Ther., 24, 563-570. PAXTON, J.W., ROWELL, FJ., RATCLIFFE, J.G., LAMBIE, D.G., NANDA, R., MELVILLE, I.D. & JOHNSON, R..
(1977). Salivary phenytoin radioimmunoassay: A simple method for the assessment of non-protein bound drug concentrations. Eur. J. clin. Pharmac., 11, 71-74. PAXTON, J.W., WHITING, B. & STEPHEN, K.W. (1977). Phenytoin concentrations in mixed, parotid and submandibular saliva and serum measured by radioimmunoassay. Br. J. clin. Pharmac., 4, 185-191. REYNOLDS, F., ZIROYANIS, P.N., JONES, N.F. & SMITH,
S.E. (1976). Salivary phenytoin concentrations in epilepsy and in chronic renal failure. Lancet, ii, 384-386. WADA, J.A., TROUPIN, A.S., FRIEL, P., REMICK, R., LEAL,
K. & PEARMAIN, J. (1978). Pharmacokinetic comparison of tablet and suspension dosage forms of carbamazepine. Epilepsia, 19, 251-255.
PHENYTOIN ABSORPTION IN PATIENTS WITH ILEOJEJUNAL BYPASS We read with interest the paper by Kennedy & Wade (1979) on phenytoin absorption in patients with ileojejunal bypass. In the discussion the authors express their
astonishment at finding a significantly shorter halflife of elimination in the bypass patients compared with the control group. Recalculation of the difference between the two means using the values
510
LETTERS TO THE EDITORS
Br. J.
supplied in the paper, gave a t value of 1.32 which at 14 degrees of freedom corresponds to a P value of 0.3-0.2. This should save the authors any speculation about the cause of a non-existent difference. R.E. SCHNEIDER & H. BISHOP Department of Therapeutics and Clinical Pharmacology, The Medical School, Edgbaston, Birmingham BI5 2TJ
clin. Pharmac. (1979), 8 Received June 11, 1979
Reference KENNEDY, M.C. & WADE, D.N. (1979). Phenytoin absorption in patients with ileojejunal bypass. Br. J. clin. Pharmac., 7, 515-518.
PHENYTOIN ABSORPTION IN PATIENTS WITH ILEOJEJUNAL PYPASS Thank you for pointing out an error in the calculated P value presented in the results of this paper (Kennedy & Wade, 1979). The significance calculated by one tail t-test with 14 degrees of freedom is, in fact, 0.10263. However, the conclusions shown in the Discussion appear to be sound. 'However, the difference was smail and a larger number of patients would be needed to be certain this difference was real.' Nowhere in the Discussion do the authors express 'astonishment' or even mild surprise.
D.N. WADE Department of Clinical Pharmacology, St Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia
Received August 13, 1979
Reference KENNEDY, M.C. & WADE, D.N. (1979). Phenytoin absorption in patients with ileojejunal bypass. Br. J. clin.
Pharmac., 7, 515-518.
