Saliva and tears alternative to serum for therapeutic drug monitoring

Drugs that are not ionizable or are un-ionized within the salivary pH range (phenytoin, carbamazepine, and theophylline) are candidates for salivary therapeutic drug monitoring (102). Salivary flow rates vary significantly between individuals and under different conditions. The use of stimulated saliva has advantage over resting saliva. The salivary flow rate, pH and sampling condition, and other pathophysiological factors may influence the concentration of a particular drug in saliva. However, under well-controlled and standardized conditions, saliva can be used as an alternative matrix for monitoring of carbamazepine, phenytoin, primidone, and ethosuximide. One report also concluded that monitoring of salivary phenytoin and carbamazepine proved to be a realistic alternative to plasma-free level monitoring because excellent correlations were found between salivary levels and serum-unbound levels of both phenytoin and carbamazepine (103). However, a poor correlation was observed between serum and salivary methadone concentration (104). Controversy also exists for valproic acid and phenobarbital (105). Nakajima et al. (106) compared tear valproic acid concentrations with total and free valproic acid concentrations in serum and concluded that the tear valproic acid concentrations correlated well with free valproic acid concentrations in serum.

Berkovitch et al. reported that there was no correlation between total or free digoxin plasma digoxin levels and salivary digoxin concentrations in children. The authors also observed no correlation between plasma gentamicin concentration and salivary levels when gentamicin was administered three times a day. In contrast, when gentamicin was administered once a day, a good correlation was found between plasma and salivary gentamicin concentrations (107). Madsen et al. (108) reported that tobramycin could not be detected in saliva within the first 6 h of therapy in patients with cystic fibrosis. On the contrary, the average indinavir concentration in plasma is 70% of the serum concentration, and saliva can be used as an alternative matrix for the therapeutic drug monitoring of indinavir (109). Ryan et al. (110) reported that despite wide inter-patient variability in saliva and serum ratio of lamotrigine, there is usually a good relation between serum and salivary concentrations of lamotrigine.

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