Experiment 352135
Worktypes
Details
| Property | Value |
|---|---|
| Pharmacology | |
| Administration route | ORAL |
| Organism | Citrus paradisi (RUTACEAE) |
| Citation | CLIFFORD,CP: ADAMS,DA: MURRAY,S: TAYLOR,GW: WILKINS,MR: BOOBIS,AR: DAVIES,DS:. (1997). THE CARDIAC EFFECTS OF TERFENADINE AFTER INHIBITION OF ITS METABOLISM BY GRAPEFRUIT JUICE.. 52(4) |
| Amount utilized | |
| Compound isolated | |
| Disease | TERFENADINE MAY LEAD TO AN INCREASE IN TERFENADINE BIOAVAILABILITY BUT THE INCREASE OBSERVED IN THIS STUDY DID NOT LEAD TO SIGNIFICANT CARDIOTOXICITY IN NORMAL SUBJECTS. OBJECTIVE: TO DETERMINE WHETHER THE PHARMACOKINETICS AND ELECTROCARDIOGRAPHIC PHARMACODYNAMICS OF TERFENADINE ARE AFFECTED BY THE CONCOMITANT ADMINISTRATION OF GRAPEFRUIT JUICE. METHODS: SIX HEALTHY VOLENTEERS WERE RECRUITED FOR A BALANCED CROSS -OVER STUDY. EACH VOLUNTEER RECEIVED 120 MG TERFENADINE 30 MIN AFTER DRINKING 300 ML OF EITHER WATER OR FRESHLY SQUEEZED GRAPEFRUIT JUICE. THE ALTERNATIVE TREATMENT WAS ADMINISTERED ON THE SECOND STUDY DAY 2 WEEKS LATER. MEASUREMENTS OF THE AREA UNDER THE TERFENADINE PLASMA CONCENTRATION-TIME CURVE MAXIMUM TERFENADINE CONCENTRATION AND THE TIME TO MAXIMUM CONCENTRATION WERE MADE, AND THE CORRECTED QT INTERVAL WAS MEASURED FROM THE SURFACE ELECTROCARDIOGRAM. RESULTS: TERFENADINE WAS QUANTIFIABLE IN PLASMA IN ALL 6 SUBJECTS ON BOTH STUDY DAYS FOR UP TO 24 H POST-DOSING. THE AUC OF TERFENADINE WAS SIGNIFICANTLY INCREASED BY CONCOMITANT GRAPEFRUIT ADMINISTRATION (MEDIAN VALUES 40.6 VS 2.1 NG.ML-1). AS WAS THE C-MAX(MEDIAN VALUES 7.2 VS 2.1 NG.ML-1). THE T-MAX WAS NOT SIGNIFICANTLY INCREASED AND THERE WAS NO SIGNIFICANT CHANGE IN THE MEDIAN QTC INTERVAL DESPITE THE INCREASED TERFENADINE LEVELS. CONCLUSION: ADMINISTRATION OF GRAPEFRUIT JUICE CONCOMITANTLY WITH TERFENADINE MAY LEAD TO AN INCREASE IN TERFENADINE BIOAVAILABILITY BUT THE INCREASE OBSERVED IN THIS STUDY DID NOT LEAD TO SIGNIFICANT CARDIOTOXICITY IN NORMAL SUBJECTS. |
| Dose amount | 300.0 ML |
| Number | 1 |
| Qualitative result | ACTIVE |
| Animal | HUMAN ADULT |
| Per unit | PERSON |
| Dose expression | DOSE |
| Extract | JUICE |
| Gender | MALE |