Absorption of ibuprofen orodispersible tablets in early postoperative phase – a pharmacokinetic study

Abstract

Objective: Patient-controlled oral analgesia has gained popularity in postoperative pain management. Anesthesia and surgery delay gastrointestinal tract function and this may therefore decrease bioavailability of drugs taken by mouth. To hasten absorption, an orodispersible ibuprofen tablet has been developed. In this study, we evaluated the pharmacokinetics and feasibility of orodispersible ibuprofen tablets in spine surgery patients.

Methods: The study design was a prospective clinical trial where each patient served as her/his own control. Fifteen patients aged 19–75 years were given two orodispersible ibuprofen 200 mg tablets the day before surgery and two more tablets immediately after surgery. Blood samples for ibuprofen concentrations were taken at intervals for 6 hours following pre- and postsurgical administration of ibuprofen.

Results: The mean preoperative area under time–concentration curve for ibuprofen (AUC_0–360) was 4806 (SD 1104) min·mg/L, and after surgery it was 2141 (583) min·mg/L (mean difference 2664, 95% CI for difference 2003 to 3325, p < .001). The mean of the maximum preoperative plasma concentration of ibuprofen was three times higher, 26.7 (7.7) mg/L, than the postoperative value of 8.6 (2.1) mg/L (mean diff. 18.1, 95% CI 13.9 to 22.4, p < .001). Times to maximum concentration were similar pre- and postoperatively at 155 (58) minutes and 169 (113) minutes (p = .67). No serious or unexpected adverse events were recorded.

Conclusions: While orodispersible ibuprofen tablets were feasible, ibuprofen absorption decreased immediately after surgery compared to the day before surgery. Thus, further studies are needed to establish the adequate initial postoperative dose.

Keywords:

• Ibuprofen
• pain
• postoperative
• pharmacokinetics
• orodispersible tablet
• back surgery

Transparency

Declaration of funding

This study had no external sponsorship/funding. The study was financially supported by the governmental VTR fund, the Hospital District of Northern Savo, Kuopio, Finland and the Finnish Cultural Foundation, Helsinki, Finland.

Author contributions: Conception and design: M.K., H.M.L., V.P.R., H.K.; analysis and interpretation of the data: A.P., M.K., H.M.L., M.L., V.P.R., H.K.; drafting of the paper: A.P., M.K., M.L., V.P.R., H.K.; revising it critically for intellectual content: A.P., M.K., H.M.L., M.L., V.P.R., H.K.; final approval of the version to be published: A.P., M.K., H.M.L., M.L., V.P.R., H.K.; all authors agree to be accountable for all aspects of the work: A.P., M.K., H.M.L., M.L., V.P.R., H.K.

Declaration of financial/other relationships

A.P., M.K., H.M.L., M.L., V.P.R. and H.K. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

The authors acknowledge medical editing and English language support from Jo Ann LeQuang and John Bisney of LeQ Medical in Angleton, TX, USA.