The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol.
BACKGROUND
Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet.


METHODS
Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-over, repeat-dose study.


RESULTS
Pharmacokinetic parameters for ibuprofen and paracetamol were similar for the combination and monotherapy tablets (values falling within the 80% to 125% acceptable bioequivalence range) except for the rate of absorption of paracetamol from the combination (tmax), which was significantly faster compared with monotherapy (median difference 10 minutes; p < 0.05). Mean plasma concentrations of both drugs were higher, earlier, following administration of the combination tablet compared with monotherapy. Mean plasma levels at 10 and 20 minutes were 6.64 microg x mL(-1) and 16.81 microg x mL(-1), respectively, for ibuprofen from the combination, compared with 0.58 microg x mL(-1) and 9.00 microg x mL-1, respectively, for monotherapy. For paracetamol, mean plasma levels at 10 and 20 minutes were 5.43 microg x mL(-1) and 14.54 microg x mL(-, respectively, for the combination compared with 0.33 microg x mL(-1) and 9.19 microg x mL(-1), respectively, for monotherapy. The rate of absorption of both ibuprofen and paracetamol was significantly delayed when the combination tablet was administered in the fed versus fasted state; median delay was 25 minutes for ibuprofen (p > 0.05) and 55 minutes for paracetamol (p < 0.001). The pharmacokinetic parameters were comparable irrespective of whether the combination tablet was given twice or three times daily; systemic exposure was, however, approximately 1.4 times greater for both drugs when given three times daily.


CONCLUSIONS
Administration of ibuprofen and paracetamol in a fixed-dose combination tablet does not significantly alter the pharmacokinetic profiles of either drug, except for enhancing the rate of paracetamol absorption, offering potential therapeutic benefits in relation to the onset of analgesia. Concentrations of both drugs reached previously reported therapeutic levels when the combination tablet was administrated in the fed or fasted state. Three times daily dosing may offer enhanced therapeutic effect for longer than twice daily dosing.
Tanner
Trevor
T
Simbec Research Ltd, Cardiff Road, Merthyr Tydfil, CF48 4DR, UK. trevor.tanner@simbec.co.uk
Aspley
Sue
S
Munn
Andrew
A
Thomas
Tracy
T
D000082:Acetaminophen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D013607:Tablets; D000082:Acetaminophen; D007052:Ibuprofen