Publication bias on clinical studies of pharmacokinetic interactions between felodipine and grapefruit juice

Plasma concentrations of a variety of drugs are known to be increased by concomitant administration of grapefruit juice (GFJ) when the drugs are administered orally. Dihydropyridine Ca channel blockers, that form one of the major categories of antihypertensive, have been studied for interactions for the longest time in research history. Especially, felodipine has been the most studied dihydropyridine drug. Although a lot of clinical research has been performed on the pharmacokinetic variations of felodipine, there has been no adequate systematic study. Therefore, publications related to felodipine-GFJ interactions were integrated and analyzed with statistical procedures of meta-analysis to characterize these clinical studies. Furthermore, funnel plots were created to validate publication bias in the data. Integration of AUC values on GFJ-administered and control groups in 12 publications revealed that felodipine is apparently affected by interaction. However, publication bias was observed in the funnel plots, and null hypothesis of no bias was rejected by Begg's test. These findings suggest that the pharmacokinetic interactions with GFJ might be overrated in the fundamental trial stage.