Intravenous vs. Oral Dose Comparison of Ibuprofen and Tramadol Combinations—Enantiomers, Metabolite, Linearity, and Sex-Related Effects: A Pharmacokinetics Randomized Clinical Trial
Bibliographic record
Abstract
Background/Objectives: Using a combination of analgesics allows for the use of lower doses of each, therefore, lowering risk of side effects. The study aims to estimate the bioavailability (pharmacokinetics of enantiomers and metabolites, as well as linearity and sex-related effects) of fixed doses combinations of Ibuprofen/Tramadol via an intravenous (IV) vs. oral route, and it is interesting to bridge the gap of equipotent doses by different routes. Methods: This was a randomized, open-label, crossover, five-period pharmacokinetics clinical trial, in which a single dose of each formulation [four different strengths of Ibuprofen 400 mg/Tramadol HCl (30, 31.5, 33, 37.5 mg), intravenous; Ibuprofen/Tramadol HCl 400 mg/37.5 mg, granules for oral solution], were administered to healthy volunteers. Enantiomers of Ibuprofen, of Tramadol, and of its main active metabolite O-desmethyl-Tramadol (M1) were measured, and pharmacokinetic parameters (maximal concentration (Cmax) and area under the concentration curve (AUC)) were estimated. Given the exploratory nature of the study, the sample size was small to provide sufficient power for comparisons of differences across all subgroups. The study was registered at Spanish register of clinical trials (REec), EudraCT code: 2017-001303-77. Results: Twelve subjects were recruited. Different patterns of rate and amount of the studied analytes are shown for oral and the several strengths of IV drugs tested. Ibuprofen, with an absolute oral bioavailability of 91%, showed an equivalent AUC of oral and IV administration. Tramadol showed an absolute oral bioavailability of 80%. Conclusions: Intravenous administration of Tramadol produces higher bioavailability (Cmax and AUClast) of the parent drug and lower of M1, than oral route. Dose normalized Cmax and AUClast of Tramadol and M1 were into the bioequivalence interval. Upon our pharmacokinetics study results, the intravenous dose of Tramadol should not be reduced when switching from oral dosing. No significant differences attributable to sex, once corrected by weight, were found.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.004 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".