Pharmacokinetic interactions of fruit juices with antihypertensive drugs in humans: A systematic review and meta-analysis

Abstract

Introduction

Fruit juice-antihypertensive drug interactions can lead to subtherapeutic or supratherapeutic outcomes. This systematic review and meta-analysis assesses such interactions and their potential clinical relevance.

Methods

PubMed, Scopus, and Science Direct databases were searched from their inception through June 2024. Eligible studies were those that investigated the effects of fruit juice on the pharmacokinetics of antihypertensive drugs. I² was used to determine heterogeneity among studies, and a random effect model was employed for meta-analysis. This review adhered to PRISMA guidelines and was registered in PROSPERO (CRD42022340159).

Results

Fifty-one studies were included. Most of them were open-label crossover trials. Grapefruit juice (GFJ), an inhibitor of organic-anion-transporting polypeptide (OATP) transporters and cytochrome P450 (CYP) 3A4, significantly decreased the AUC and C_max of aliskiren and celiprolol by approximately 80–90 %. Conversely, the AUC and C_max of calcium channel blockers decreased with variable degrees when co-administered with GFJ. Apple and orange juices have comparable effects on certain medications. Most studies had small sample sizes and were of moderate quality. Hemodynamic effects were not assessed in most studies; thus, the clinical significance of these interactions remains uncertain and should be further investigated.

Conclusion

Co-administration of fruit juice with antihypertensive drugs can result in an increase or decrease in drugs’ bioavailability, depending on the drugs’ metabolism route and the involvement of transporters. Though further studies are needed to confirm clinical relevance in hypertensive patients, it is advised to avoid co-consumption of fruit juice with drugs showing significant changes in pharmacokinetic parameters to prevent subtherapeutic or supratherapeutic effects.