THE EFFECT OF PIRENZEPINE ON GASTRIC-EMPTYING AND SALIVARY FLOW-RATE - CONSTRAINTS ON THE USE OF SALIVA PARACETAMOL CONCENTRATIONS FOR THE DETERMINATION OF PARACETAMOL PHARMACOKINETICS

1 The effects of pirenzepine on gastric emptying, salivary flow and saliva paracetamol concentrations were investigated in healthy volunteers. 2 Pirenzepine significantly reduced the area under the saliva flow-time curves (7.29 +/- 3.30 g min-1 h without pirenzepine; 4.19 +/- 2.59 g min-1 h with pirenzepine, P < 0.01). Pirenzepine had no significant effect on plasma paracetamol C(max) (17.5 +/- 7.8-mu-g ml-1 without pirenzepine; 12.6 +/- 7.7-mu-g ml-1 with pirenzepine), plasma t(max) (0.2 h (0.2-0.8 h) without pirenzepine; (0.2 h 0.2-0.8 h) with pirenzepine) and plasma AUC(0,6 h) (32.3 +/- 7.2-mu-g ml-1 h without pirenzepine; 30.3 +/- 6.5-mu-g ml-1 h with pirenzepine). 3 Mean ratios of saliva:plasma paracetamol AUC (1.06 +/- 0.24 without pirenzepine; 1.84 +/- 0.48 with pirenzepine, P < 0.001) and saliva:plasma paracetamol C(max) (1.7 +/- 1.0 without pirenzepine; 6.5 +/- 2.7 with pirenzepine, P < 0.01) were significantly increased by pirenzepine pretreatment, but there was a poor correlation between the percentage change in the area under the saliva flow-time curve and the percentage change in saliva paracetamol AUC (r = 0.47, P = 0.21). 4 The findings suggest that a) pirenzepine is a more selective antagonist of the muscarinic receptors in salivary glands than those in gastric smooth muscle and b) caution is required when using saliva paracetamol concentrations to determine the pharmacokinetics of the drug in the presence of other agents which may influence salivary flow rate.