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Predictive performance of three practical approaches for grapefruit juice‐induced 2‐fold or greater increases in AUC of concomitantly administered drugs
Author(s) -
Takahashi M.,
Onozawa S.,
Ogawa R.,
Uesawa Y.,
Echizen H.
Publication year - 2015
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12231
Subject(s) - grapefruit juice , fold (higher order function) , medicine , pharmacology , pharmacokinetics , computer science , programming language
Summary What is known and objective Clinical pharmacists have a challenging task when answering patients’ question about whether they can take specific drugs with grapefruit juice ( GFJ ) without risk of drug interaction. To identify the most practicable method for predicting clinically relevant changes in plasma concentrations of orally administered drugs caused by the ingestion of GFJ , we compared the predictive performance of three methods using data obtained from the literature. Methods We undertook a systematic search of drug interactions associated with GFJ using MEDLINE and the Metabolism & Transport Drug Interaction Database ( DIDB version 4.0). We considered an elevation of the area under the plasma concentration‒time curve ( AUC ) of 2 or greater relative to the control value [ AUC ratio ( AUCR ) ≥ 2·0] as a clinically significant interaction. Results and discussion The data from 74 drugs (194 data sets) were analysed. When the reported information of CYP 3A involvement in the metabolism of a drug of interest was adopted as a predictive criterion for GFJ ‒drug interaction, the performance assessed by positive predictive value ( PPV ) was low (0·26), but that assessed by negative predictive value ( NPV ) and sensitivity was high (1·00 for both). When the reported oral bioavailability of ≤0·1 was used as a criterion, the PPV improved to 0·50 with an acceptable NPV of 0·81, but sensitivity was reduced to 0·21. When the reported AUCR was ≥10 after co‐administration of a typical CYP 3A inhibitor, the corresponding values were 0·64, 0·79 and 0·19, respectively. What is new and conclusion We consider that an oral bioavailability of ≤0·1 or an AUCR of ≥10 caused by a CYP 3A inhibitor of a drug of interest may be a practical prediction criterion for avoiding significant interactions with GFJ . Information about the involvement of CYP 3A in their metabolism should also be taken into account for drugs with narrow therapeutic ranges.