Pharmacokinetics and anaesthetic effects of propofol‐PM: a novel water soluble propofol formulation
Bibliographic record
Abstract
We have investigated the use of amphiphilic diblock copolymers of poly (N-vinyl-2-pyrrolidone) and poly-(d,l-lactide), PVP-PLA, to dissolve propofol inside micelles (30–60 nm) – Propofol-PM. We compared the pharmacokinetics (PK) of propofol in blood and plasma when administered as 1% Diprivan and as three 1% solutions reconstituted from Propofol-PM 7, 10 and 12% respectively. We also undertook a preliminary pharmacodynamic (PD) study. Forty male Sprague–Dawley rats (325 ± 10 g) were randomly allocated to one of eight groups (five rats/group). Ten rats were used for each of the four propofol formulations: five rats for the collection of whole blood and five for plasma. The rats were anaesthetised with isoflurane and both jugular veins exposed. Isoflurane was then discontinued. When the animals responded to a hind paw pinch, they received propofol 10 mg.kg (1 ml.kg over 1 min) via the jugular vein. Blood samples were collected at 1, 3, 5, 7.5, 10, 15, 30, 60 and 75 min after injection. A PK model was constructed using nonmem software. Animal weight, sample matrix (blood or plasma) and propofol formulation (Diprivan, Propofol-PM 7, 10 and 12%) were evaluated as model covariates. In a separate small PD study, the times of the recovery endpoints (leg withdrawal, first movement, righting) were compared for the four propofol formulations. All experiments were conducted in accordance with guidelines from the Canadian Council on Animal Care and the Use of Laboratory Animals, and a certificate of conformity granted. The optimal PK model had two compartments and incorporated sample matrix and propofol formulation as dichotomous covariates (Fig. 1). Sample matrix was applied to all structural parameters. An influence of propofol formulation was observed for all structural model parameters (excluding distributional clearance) but only when plasma was used as the sample matrix. The effect of formulation was not apparent when whole blood concentrations of propofol were measured. The average model predicted profiles. Error bars show ± 1 SD. The whole blood PK of Propofol-PM did not differ from that observed with Diprivan. We observed lower propofol concentrations in plasma samples after Propofol-PM administration than after Diprivan but the quantity of the copolymer in the Propofol-PM formulations did not influence the PK. Although there was no statistically significant difference in any of the recovery endpoints, the number of animals in the PD study was small (n = 4–6 per formulation) and there was a high degree of variability. Hence, the PD study was likely underpowered to detect small differences and must be regarded as preliminary.
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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".