Phenytoin and phenobarbital concentrations in saliva and plasma measured by radioimmunoassay

Abstract

Saliva and plasma levels of phenytoin (DPH) and phenobarbital (PB) in a series of epileptic patients were compared by means of a radioimmunoassat (RIA) that required only 10 mul of saliva or plasma. There was an excellent linear relation (r = 0.98) between the logarithms of the concentrations of DPH in the two fluids. The ratio saliva/plasma was remarkably constant at 0.10 and was unaffected by varying levels of PB. The ratio was close to the fraction of DPH reported unbound in plasma at 37 degrees. PB plasma and saliva levels were also closely related (r = 0.98 for logarithm of plasma and saliva levels). This relation was nonlinear [plasma ocncentration = 4.43 X (salivary concentration)0.86], but could be approximated by the ratio plasma/saliva = 3.4. The simplicity of sample collection and the sensitivity of the RIA procedure suggest that clinical monitoring of these anticonvulsant levels may be carried out by RIA on saliva samples.

Compliance with anticonvulsant therapy in a hospital clinic and in the community.

“…Analysis by gas chromatographic methods, such as the one used here, demands considerable technical expertise and is timeconsuming. Radioimmunoassay (Cook et al, 1975) is faster but more expensive. Quantitative enzyme immunoassay (Bastiani, Phillips, Schneider & Ullman, 1973) requiring only a spectrophotometer, may prove the simplest method but is at present very expensive.…”

“…Saliva phenytoin concentrations provide a reliable index of concentration in plasma (Bochner, Hooper, Sutherland, Eadie & Tyrer, 1974) and this is also true of phenobarbitone (Cook, Amerson, Poole, Lesser & O'Tuama, 1975).…”

Relationship Between Serum and Saliva Chloramphenicol Concentrations

“…This conclusion is based upon the negligible improvement in correlation (0.80 to 0.81) achieved when free serum CAP concentration rather than total concentration was correlated with saliva CAP concentration. Phenytoin, which is highly but variably bound to serum proteins, demonstrates a greater correlation between free serum and saliva concentrations than between total serum and saliva concentrations (4). The low and relatively constant binding of CAP observed in this study (43.7 ± 5.7%) would not be expected to be a major source of variation in the saliva-to-serum drug concentration ratio.…”

Saliva carbamazepine and phenytoin level monitoring.

“…Twenty of the children were receiving CBZ, of whom 16 were using tablets and 4 syrup formulations. Fifteen children were receiving DPH, and of these, 9 used chewable tablets, 3 Saliva was assayed for CBZ by a modification4 of the gas-liquid chromatography method for serum described by Least et al. 5 and for DPH by radioimmunoassay6 using antisera supplied by Dr G W Aherne, University of Surrey.…”

“…The need for regular monitoring of phenytoin (DPH) levels in epilepsy is accepted, and a good case can be made for the routine monitoring of carbamazepine (CBZ) levels.' Saliva CBZ and DPH levels in mixed saliva show a good correlation with plasma levels2 3 and may provide a convenient and non-invasive means of drug level monitoring in children. An optimal therapeutic response with minimal risk of adverse effects is likely to be achieved in a majority of children if saliva CBZ concentrations are maintained within 5-15 ,tmol/l (1-2-3X5 ,g/ml) and if saliva DPH concentrations are within [2][3][4][5][6][7][8][9][10] ,umol/l (5-25 Vglml).…”