Pharmacokinetics and saliva secretion of paracetamol

A preliminary pharmacokinetic study of paracetamol was carried out in Nigerians for whom it is normal to consume paracetamol or its combination during almost any type of symptoms. After a single oral dose of 1000 mg of the drug to eight adult male volunteers, paracetamol was measured in plasma and saliva using high-performance liquid chromatography. The plasma profile showed a biexponential decline after peak absorption. Some of the pharmacokinetic parameters compared with previous results from Caucasians and Asians although some differences were observed. The absorption of paracetamol was rapid with mean tmax of 0.875 +/- 0.44 h (range, 0.5-1.5 h) and was 20 times faster than elimination rate. The Cmax varied between 11.46 and 26.44 microg mL(-1) with three of the subjects having Cmax greater than the 20 microg mL(-1) limit for therapeutic level. The elimination half-life was slightly longer than previous reports, with four subjects having t(1/2) above 3 h. The t(1/2) was found to correlate significantly (p < 0.01) with the mean residence time (MRT), an indication that MRT can be used where t(1/2) cannot be evaluated. The oral clearance was slightly lower (about 25%) than earlier reports in some Caucasians and Asians. The absorption parameters from saliva (Cmax, tmax, AUC and saliva levels) correlated well (r = 0.88 to 0.999) with those from plasma. The plasma levels were higher than saliva in all the subjects studied with variable S/P ratio of 0.64 +/- 0.1 in contrast to ealier reports of S/P ratios above unity. In conclusion, the pharmacokinetics of paracetamol in Nigerians shows possibility of higher plasma levels and slower clearance from the body.