Bioavailability of two new formulations of paracetamol, compared with three marketed formulations, in healthy volunteers.
The aim of this study was to compare the main pharmacokinetic characteristics of two new paracetamol formulations, powder sachet and tablet, with that of three commercially available paracetamol formulations: two conventional solid tablets and one effervescent tablet. Twelve healthy volunteers participated in an open, single dose (paracetamol 1,000 mg), randomized, five-way, crossover study. Formulations studied included: formulation A: 2 x 500 mg paracetamol tablets (Laboratorios Belmac S.A.); formulation B: 1 x 1,000 mg paracetamol powder sachets (Laboratorios Belmac, S.A.); formulation C: 2 x 500 mg paracetamol film-coated tablets (Panadol, SmithKline Beecham); formulation D: 2 x 500 mg paracetamol tablets (Tylenol, McNeil); and formulation E: 1 x 1,000 mg effervescent paracetamol tablets (Efferalgan, UPSA). The primary variables were area under the plasma concentration time curve extrapolated to infinity (AUC(0-infinity)), maximum plasma concentration (Cmax), and time to maximum plasma concentration (tmax). Mean AUC(0-infinity) ranged from 52.6 (B) to 56.3 microg x h/ml (D); mean Cmax varied between 17.98 (C) and 20.73 microg/ml (E); mean tmax ranged from 0.40 (E) to 0.88 h (C); and median t(1/2) varied between 2.65 (C) and 2.81 h (A). Formulations A, B and E showed significantly shorter tmax than formulation C. The tmax and Cmax values found for formulations A and B were very similar to that found for E, an effervescent tablet formulation. In conclusion, the two new formulations of paracetamol tested in this study were absorbed rapidly after a single oral dose in healthy volunteers, similar to an effervescent paracetamol formulation and significantly faster than two ordinary commercialized paracetamol tablets.
Laboratorios Belmac, Madrid, Spain. nfernandez@belmac.com
F J
FJ
Sevilla-Tirado
E B
EB
González-Vallejo
A C
AC
Leary
H J
HJ
Breedt
V J
VJ
Hyde
N
N
Fernández-Hernando
D000082:Acetaminophen / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D011208:Powders; D013607:Tablets
D018712:Analgesics, Non-Narcotic; D011208:Powders; D013607:Tablets; D000082:Acetaminophen