Pharmacokinetics of ibuprofen sodium dihydrate and gastrointestinal tolerability of short-term treatment with a novel, rapidly absorbed formulation.
OBJECTIVE
This paper describes four studies investigating the dissolution, plasma pharmacokinetics and safety of a novel, fast-acting ibuprofen formulation, ibuprofen sodium dihydrate.


METHODS
Four separate studies investigated: the in vitro dissolution rates of ibuprofen sodium dihydrate (at pH 1.2, 3.5 and 7.2); the bioavailability of ibuprofen sodium dihydrate (in two pharmacokinetic studies; combined n = 38) compared with conventional ibuprofen, ibuprofen lysinate, ibuprofen arginate and ibuprofen liquagels (all 2 x 200 mg ibuprofen); and the gastroduodenal tolerance of ibuprofen sodium dihydrate and ibuprofen arginate (both 2 x 200 mg ibuprofen t.i.d.) in an endoscopy safety study, where endoscopy was performed at baseline and at the end of each treatment period using a five-point scale to assess the integrity of the gastric and duodenal mucosa.


RESULTS
Ibuprofen sodium dihydrate dissolved significantly more rapidly at pH 1.2, 3.5 and 7.2 than conventional ibuprofen, ibuprofen lysinate and ibuprofen liquagels. Ibuprofen sodium dihydrate had similar C(max) to ibuprofen lysinate and ibuprofen liquagels and significantly higher Cmax than conventional ibuprofen (p = 0.002). The mean plasma concentration for ibuprofen sodium dihydrate was significantly higher than for conventional ibuprofen (p = 0.028) 10 minutes post-dose and the t(max) for ibuprofen sodium dihydrate was reached significantly earlier than for conventional ibuprofen (p = 0.018). All three formulations were bioequivalent according to the acceptable boundaries (90% confidence intervals). No statistically significant difference was observed between the ibuprofen formulations in terms of adverse events and specifically with respect to hemorrhagic scores; 41 (46.0%) adverse events (AEs) occurred after administration of ibuprofen sodium dihydrate, and 46 (52.9%) after ibuprofen arginate. One occurrence of an invasive ulcer was observed after administration of ibuprofen arginate.


CONCLUSIONS
The new formulation of ibuprofen sodium dihydrate dissolves quickly in vitro, has the same extent of absorption as other fast-acting ibuprofen formulations, and is absorbed into plasma more rapidly than conventional ibuprofen. In addition, the present studies suggest that the tolerability and safety profile of ibuprofen sodium dihydrate is comparable to existing ibuprofen formulations.
Sörgel
F
F
Institute for Biomedical and Pharmaceutical Research, Nüremberg-Heroldsberg, Germany. ibmp@osn.de
Fuhr
U
U
Minic
M
M
Siegmund
M
M
Maares
J
J
Jetter
A
A
Kinzig-Schippers
M
M
Tomalik-Scharte
D
D
Szymanski
J
J
Goeser
T
T
Toex
U
U
Scheidel
B
B
Lehmacher
W
W
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen