Red wine–cisapride interaction: Comparison with grapefruit juice
Bibliographic record
Abstract
OBJECTIVES: Our objective was to compare the interactions of red wine and grapefruit juice with cisapride. METHODS: The oral pharmacokinetics of cisapride, its norcisapride metabolite, and electrocardiographic QTc interval were determined over a 24-hour period after administration of cisapride 10 mg with 250 mL grapefruit juice, red wine (cabernet sauvignon), or water in a randomized 3-way crossover study in 12 healthy men. RESULTS: The cisapride area under the concentration-time curve (AUC) and the maximum plasma drug concentration after single-dose administration (C(max)) with grapefruit juice were 151% (P <.01) and 168% (P <.001), respectively, of those with water. The increase in cisapride AUC and C(max) was variable among individuals; however, cisapride AUC and C(max) were enhanced by the same proportion. The time to reach maximum concentration after drug administration (t(max)) and the apparent elimination half-life (t((1/2)) for cisapride and the pharmacokinetics of norcisapride were not altered. Norcisapride/cisapride ratios were reduced. Cisapride AUC and C(max) with red wine were 115% (difference not statistically significant) and 107% (difference not statistically significant), respectively, of those with water. The cisapride t(max) was slightly longer. Cisapride t((1/2)) and norcisapride pharmacokinetics were not different. The norcisapride/cisapride ratio at cisapride C(max) was lower. One subject had a doubling in cisapride AUC and C(max) and a decrease in norcisapride/cisapride ratios with red wine and also had the largest interaction with grapefruit juice. QTc interval was unchanged in all treatment groups and individuals. CONCLUSIONS: A single glass of grapefruit juice produced an individual-dependent variable increase in the systemic availability of cisapride by inhibition of intestinal cytochrome P450 3A4 (CYP3A4) activity. The identical volume of red wine caused only minor changes in cisapride pharmacokinetics despite some inhibition of CYP3A4 in most individuals. However, even this amount of red wine may cause a marked interaction similar to that for grapefruit juice in individuals with a preexisting high intestinal CYP3A4 content.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 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; both teacher heads agree on what is shown here.
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".