Comparative Efflux of Saquinavir, Ritonavir and Lopinavir from Primary Human Cells
Bibliographic record
Abstract
Therapeutic drug monitoring is an important element in the management of drug treatment in HIV-1 infected patients. We have examined the effect of temperature on the egress of HIV-1 protease inhibitors from primary T lymphocytes to determine optimum conditions to be adopted in the processing of blood samples in order to accurately estimate intracellular or plasma drug concentrations. Peripheral blood mononuclear cells or U937 cells were incubated with radiolabelled saquinavir, ritonavir or lopinavir at a concentration of 1 μM. The cells were washed and resuspended in RPMI medium (without radiolabelled drug) and further incubated at 37°C, room temperature (21°C) or at 4°C. We observed that release of drug ensued upon the removal of cells from bathing media containing drug, with the rate of efflux being slower at 4°C and fastest at 37°C for all the protease inhibitors. There was a more rapid efflux of saquinavir and ritonavir than lopinavir from both cultured monocytic and primary human cells. The rank order of the partition coefficient of the drugs were lopinavir > saquinavir > ritonavir. All factors that may limit optimal estimation of cell-associated drug concentrations must be considered so that intracellular concentrations of drug can be accurately estimated. Keywords: Protease inhibitor, HIV-1, release, peripheral blood, saquinavir, ritonavir, lopinavir, Therapeutic drug monitoring, plasma drug concentrations, Peripheral blood mononuclear cells, cell-associated drug concentrations, Highly active antiretroviral therapy (HAART), non-nucleoside, lymphocytes, Multi-drug resistance, breast cancer resistance protein (BCRP), lipophilicity, anti-coagulated, Octanol-Saline Partition Coefficient, efflux proteins, drug-containing bathing media
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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) | 0.001 | 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".