Absence of circadian variation in the pharmacokinetics (PK) of lopinavir/ritonavir (LPV/R) in a once-daily (QD) dosing regimen in hiv-1-infected subjects
Bibliographic record
Abstract
Background Previous studies suggest a circadian phase dependency in the PK of protease inhibitors. This may have practical implications, especially for qd regimens. This study explored the PK of LPV/r 800/200 mg qd after am versus pm dosing. Methods A randomized two-way cross-over study in HIV+ subjects taking LPV/r bid + 2 NRTIs. 24h PK were assessed after 2 weeks of LPV/r qd at 8 am and 7 pm, resp. LPV/r was taken with a standardized meal (800 kCal, 30% from fat) after fasting for 5 h. LPV/r concentrations were measured by LC/MS/MS. PK were analyzed by noncompartmental methods. Results 12 subjects completed the study (all men, mean age/weight 44 yrs/80 kg). The median (IQR) LPV AUC24h, Cmax and C24h after am and pm dosing was 143 (100-235) h*mg/L, 12.8 (8.8-19.6) mg/L, 1.2 (0.6-2.4) mg/L, and 171 (122-230) h* mg/L, 12.9 (8.4-16.9) mg/L, 1.0 (0.4-1.7) mg/L, resp. The intra- and intersubject variability in the LPV AUC24h was 19 and 39%, resp. The geometric mean ratio (GMR, am/pm) and 90% CI of the LPV AUC24h, Cmax, and C24h was 0.91 (0.78-1.05), 1.09 (0.99-1.21), and 1.24 (0.78-1.97), resp. For 11/12 subjects RTV concentrations remained below 2.1 mg/L. The GMR (90% CI) of the RTV AUC24h, Cmax, and C24h was 0.94 (0.81-1.11), 1.35 (1.09-1.68), and 1.04 (0.7–1.54), resp. Conclusion No clinically relevant differences were observed in the PK of LPV/r after am or pm dosing with food. This suggests that LPV/r qd can be taken in the morning or evening, which may facilitate adherence. Clinical Pharmacology & Therapeutics (2004) 75, P35–P35; doi: 10.1016/j.clpt.2003.11.133
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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 | 0.001 | 0.002 |
| 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) | 0.001 | 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 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".