Effect of perfused rat mandibular-gland pHI on the ratio of procainamide concentration in saliva to that in venous effluent.

The saliva to venous-effluent concentration ratio (S/E ratio) for procainamide (PA) was determined and compared with the ratio calculated by using the intracellular pH value of glandular cells. Exposed mandibular gland was perfused in situ with Krebs-Ringer bicarbonate buffer containing PA (10-100 micrograms/ml) and acetylcholine (ACh, 0.1 to 10 microM) or pilocarpine (10 microM). These perfusion conditions maintained almost normal physiological function of the mandibular gland throughout the perfusion period of 60 min, since the salivary Na+ and K+ concentrations were kept at almost constant levels, comparable with those reported in vivo, and the salivary flow, pH and protein level were also stabilized. Under fixed stimulation conditions with 1 microM ACh or 10 microM pilocarpine, the perfusate PA concentration ranging from 20 to 100 micrograms/ml did not affect the S/E ratio (approximately 0.3). There was a negative correlation between the S/E ratio and salivary pH when stimulated with 0.1 to 10 microM ACh. However, Matin's equation [S. B. Matin et al., Clin. Pharmac. Ther. 16, 1052 (1974)] employing venous effluent and salivary pH values did not explain fully these observed ratios. In contrast, Borzelleca's model [J. F. Borzelleca and J. W. Putney, J. Pharmac. exp. Ther. 174, 527 (1970)] for salivary drug transport using intracellular pH of the mandibular gland cells predicted S/E ratios relatively close to the observed values when the gland was perfused at pH 7.4 or 8.0.