A New Rapidly Absorbed Paracetamol Tablet Containing Sodium Bicarbonate. I. A Four-Way Crossover Study to Compare the Concentration–Time Profile of Paracetamol from the New Paracetamol/Sodium Bicarbonate Tablet and a Conventional Paracetamol Tablet in Fed and Fasted Volunteers

Abstract

The primary objective of this four-way crossover study was to compare the concentration-time profile of paracetamol from a new rapidly absorbed paracetamol tablet containing sodium bicarbonate (PS) with a conventional paracetamol tablet (P), in a panel of 28 fed and fasted healthy volunteers. The results demonstrated that paracetamol was absorbed more rapidly from tablets containing sodium bicarbonate compared to conventional tablets, as indicated by a shorter tmax in both the fed and fasted state and a higher Cmax in the fasted state. The two formulations were bioequivalent with respect to area under curve (AUC). Food did not affect the extent of absorption from either formulation, as indicated by AUC, however, food did reduce the rate of absorption from both formulations, as indicated by a longer tmax and a lower Cmax. Metabolic activation of paracetamol to its oxidation metabolites, as assessed by combined partial clearances to subsequent secondary metabolites cysteine and mercapturic acid conjugates, indicated that the two formulations were bioequivalent in this respect.

Pharmacokinetics of an Oral Drug (Acetaminophen) Administered at Various Times Relative to Subcutaneous Injection of Pramlintide in Subjects With Type 2 Diabetes

“…In the present study, pramlintide was administered immediately before a meal (breakfast) 33 . The changes in C max and T max between acetaminophen administered in nonfasting and fasting conditions in this study are consistent with previous reports demonstrating that the pharmacokinetics of acetaminophen are affected by food 27 , 28 . Although the impact of food on acetaminophen pharmacokinetics is well established in the literature, 24 – 28 there are no recommendations for dose adjustments when taken with food.…”

Comparison of a novel fast-dissolving acetaminophen tablet formulation (FD-APAP) and standard acetaminophen tablets using gamma scintigraphy and pharmacokinetic studies

“…The mean C max was slightly higher with FD-APAP, but the range of individual C max values for standard acetaminophen was below the maximum value (mean: 18 ± 10 μg/ mL, range: 8-49 μg/mL) previously observed for standard acetaminophen in the fasted state 13 . Similar pharmacokinetic results have been found in an additional in vivo study involving 30 healthy volunteers that compared the same FD-APAP to a generic standard 500 mg acetaminophen tablet product available in Australia (Herron; unpublished data).…”

“…It has previously been shown that in vivo-in vitro correlation methods may be used successfully to relate the in vitro dissolution characteristics of different products to their in vivo release and therapeutic outcomes 12 . An acetaminophen tablet that contains 630 mg of sodium bicarbonate has been shown to be absorbed twice as fast as standard acetaminophen tablets [9][10][11][12][13] . This faster rate of absorption is attributed to an increase in the disintegration rate and also an accelerated gastric emptying rate that leads to a swifter transport of acetaminophen to the small intestine where absorption takes place 10 .…”

Biowaiver monographs for immediate release solid oral dosage forms: Acetaminophen (paracetamol)

“…[37], [44], [72], [83] In vivo dissolution of IR tablets in media simulating the contents of the GI lumen in the fasting state is usually rapid. [68], [84], [85] The same is true in media simulating the fed state conditions in the small intestine.…”