Comparative Bioavailability Study of Two Ibuprofen Preparations after Oral Administration in Healthy Volunteers

Abstract

The bioavailability of a new ibuprofen (2-(p-isobutylphenyl)propionic acid, CAS 15687-27-1) preparation was compared with a reference preparation of the drug in 23 healthy male volunteers, aged between 19 and 27. A single dose of 400 mg was given orally in the fasted state, using a randomized two-way crossover study. A washout period of two weeks separated both treatment periods. Ibuprofen plasma levels were determined by means of a validated HPLC method (UV detector). Values of 154.48 +/- 53.27 microg x h/ml (95 % confidence interval CI: 133.50-177.03) for the test, and 140.86 +/- 44.82 microg x h/ml (95% CI: 122.53-159.16) for the reference preparation AUC(0-infinity) demonstrate a nearly identical extent of drug absorption. Maximum plasma concentrations Cmax of 39.53 +/- 7.11 microg/ml (95 % CI: 35.97-41.78) and 37.71 +/- 8.67 microg/ml (95% CI: 33.37-40.46) achieved for the test and reference preparations did not differ significantly. AUC(0-infinity) and Cmax ratios (90% CI) were within the 80-125% interval required for bioequivalence as stipulated in the current international regulations of the European Agency for the Evalution of Medicinal Products and the Food and Drug Administration. Therefore it is concluded that the new ibuprofen preparation is therapeutically equivalent to the reference preparation for both, the extent and the rate of absorption, after single dose administration in healthy volunteers.

Linking the Gastrointestinal Behavior of Ibuprofen with the Systemic Exposure between and within Humans—Part 1: Fasted State Conditions

“…The observed plasma T max values are on the range of literature values (0.4 to 4 h) for a wide range of ibuprofen doses and immediate-release formulations, even if in most studies the average value is around 2 h. Only one subject showed an extreme plasma T max value of 8 h; all of the other subjects presented values in the range mentioned in the literature, so a delay in plasma T max caused by intubation does not seem supported by the experimental data. Nevertheless, individual values can show a wide range of values in a fasted state from 0.25 to 5 h with immediate-release tablets . These same authors reported plasma C max values from 30 to 36 μg/mL for a 400 mg ibuprofen dose in line with our observed data.…”

“…Nevertheless, individual values can show a wide range of values in a fasted state from 0.25 to 5 h with immediate-release tablets. 30 These same authors reported plasma C max values from 30 to 36 μg/mL for a 400 mg ibuprofen dose in line with our observed data. Apparent oral distribution volumes and clearances (V/F and CL/F, respectively) are, as well, consistent with the ranges of reported values (V/F from 7.7 to 14.7 L and CL/F from 2.87 to 3.6 L/h).…”

Society for Obstetric Anesthesia and Perinatology: Consensus Statement and Recommendations for Enhanced Recovery After Cesarean

“…[78][79][80][81][82][83][84] Multimodal Analgesia (Class I, Level A, High-Grade Level of Evidence) Initiating multimodal analgesia includes administration of intrathecal morphine (50-150 µg) or epidural morphine (1-3 mg); nonopioid analgesia, for example, nonsteroidal anti-inflammatory drugs and acetaminophen (started in the operating room unless contraindicated); and supplemental local anesthetic wound infiltration or truncal blocks in select cases (eg, if unable to receive the above-recommended drugs). 20,38,85,86 An emphasis on regular scheduled nonopioid analgesia commencing before the onset of pain (ie, immediately after delivery of fetus and not upon first pain request) should be central in these multimodal analgesic regimens.…”

“…[112][113][114][115] These goals are accomplished by low-dose long-acting neuraxial opioids such as morphine (see "Intraoperative" section), scheduled nonsteroidal anti-inflammatory drugs, and scheduled acetaminophen. 85,86,[116][117][118][119] Local anesthetic techniques, including wound infiltration, transversus abdominis plane (TAP), and quadratus lumborum blocks (QLB) should also be leveraged when indicated (Table 2).…”

Ibuprofen blood plasma levels and onset of analgesia

“…Pharmacokinetic studies of ibuprofen (free acid) found that maximal analgesic efficacy was achieved within 1–2 h of dosing (14–18). This relatively slow onset of action led to the development of new formulations, such as fast‐dissolving oral preparations of ibuprofen salts and gelatine capsules containing solubilised ibuprofen, which have faster absorption (T max ) and increased peak plasma concentrations (C max ) over standard ibuprofen film‐coated tablets (17,19–23).…”