SALIVARY LEVELS AS A GUIDE TO PLASMA LEVELS

Predictable or unpredictable - the answer lies in the ionisation Groups of patients or volunteers were given various doses of a range of drugs for plasma and salivary level determinations: phenytoin (diphenylhydantoin), phenobarbitone, antipyrine, propranolol, pethidine (meperidine), tolbutamide and chlorpropamide. Among the non-ionised or very weakly ionised drugs the salivary I plasma (SIP) ratios were very stable: phenytoin 0.13 (± 0.0 I); phenobarbitone 0.41 (± 0.03); antipyrine 0.92 (± 0.02), and for this last drug when salivary flow·was trebled (from about 2 to 6mll min) the SIP ratio did not significantly change (0.95 to 0.92). However, with drugs which were largely ionised the salivary levels showed very poor correlation to plasma levels and were in fact directly dependent on salivary pH, which in turn is almost entirely dependent on salivary flow. With propranolol the SIP ratio varied from 0.18 to 2.63. In a single subject, an increase in flow rate of2.3mllmin (and a pH increase of 0.35) halved the salivary concentration. With chlorpropamide the SIP ratio ranged between 0.009 to 0.026 and correlated directly with salivary pH. Five factors determine the SIP ratio of any drug, all but 1 of which - salivary pH - remain virtually constant. Thus the non­ionised drugs (or very weak acids and bases), unaffected by pH, can provide predictable results. The ionised drugs, however, susceptible as they are to minor pH changes, cannot be used for calculating plasma levels unless one can standardise the salivary flow and pH, and one knows the SI P ratio under those conditions. Mucklow, J.C. et al.: Clinicai Pharmacoiogy and Therapeutics 24: 563 (Nov! 97R)

INPHARMA 25th November. 1978 p14