A five way crossover human volunteer study to compare the pharmacokinetics of paracetamol following oral administration of two commercially available paracetamol tablets and three development tablets containing paracetamol in combination with sodium bicarbonate or calcium carbonate.
This report concerns a single dose randomized five way crossover study to compare the pharmacokinetics of paracetamol from two commercially available paracetamol (500 mg) tablets and three different development paracetamol (500 mg) tablet formulations containing either sodium bicarbonate (400 mg), sodium bicarbonate (630 mg) or calcium carbonate (375 mg). The results demonstrated that addition of sodium bicarbonate (630 mg) to paracetamol tablets, increased the rate of absorption of paracetamol relative to conventional paracetamol tablets and soluble paracetamol tablets. Addition of sodium bicarbonate (400 mg) to paracetamol tablets increased the absorption rate of paracetamol relative to conventional paracetamol tablets, but there was no difference in the rate of absorption compared to soluble paracetamol tablets. Inclusion of calcium carbonate (375 mg) to paracetamol tablets had no effect on absorption kinetics compared to the conventional paracetamol tablet. The faster absorption observed for the sodium bicarbonate formulations may be as a result of an increase in gastric emptying rate leading to faster transport of paracetamol to the small intestine where absorption takes place.
Grattan
T
T
SmithKline Beecham Consumer Healthcare, Weybridge, Surrey, UK. tim.j.grattan@sb.com
Hickman
R
R
Darby-Dowman
A
A
Hayward
M
M
Boyce
M
M
Warrington
S
S
D000082:Acetaminophen / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000863:Antacids / Q000494:pharmacology*; D019540:Area Under Curve; D002119:Calcium Carbonate / Q000494:pharmacology*; D018592:Cross-Over Studies; D005079:Excipients; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D017693:Sodium Bicarbonate / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013607:Tablets
D018712:Analgesics, Non-Narcotic; D000863:Antacids; D005079:Excipients; D013607:Tablets; D000082:Acetaminophen; D017693:Sodium Bicarbonate; D002119:Calcium Carbonate