| Disease | THE PHARMACOKINETICS OF DIGOXIN WERE INVESTIGATED IN A SINGLE-BLIND, PLACEBO-CONTROLLED PARALLEL STUDY. AFTER THE ACHIEVEMENT OF STEADY STATE FOR DIGOXIN ON DAY 5, HEALTHY VOLUNTEERS RECEIVED DIGOXIN (0.25 MG/D) EITHER WITH PLACEBO (N=12) OR
WITH 900 MG/D LI160 (N=13) FOR ANOTHER 10 DAYS. DIGOXIN CONCENTRATION PROFILES ON DAY 5 WERE COMPARED WITH DAY 6 (SINGLE-DOSE INTERACTION) AND DAY 15 (TENTH DAY OF CO-MEDIACATION). THERE WAS A HIGHLY SIGNIFICANT COMBINED-DAY-AND-GROUP EFFECT
FOR DIGOXIN AREA UNDER THE PLASMA CONCENTRATION-TIME CURVE [AUCO(0-24); P=.0001], PEAK CONCENTRATION IN PLASMA (CMAX; P=.0001), AND PLASMA DRUG CONCENTRATION AT THE END OF A DOSING INTERVAL (P=.0003) BY TWO-WAY ANOVA. NO STATISTICALLY
SIGNIFICANT CHANGE WAS OBSERVED AFTER THE FIRST DOSE OF HYPERICUM EXTRACT [AUC(0-24) AT DAY 6 OF 18.1 + 2.9 UG. H/L AND 17.7 + 3.0 UG.H/L, MEAN + SD FOR PLACEBO AND HYPERICUM GROUP, RESPECTIVELY]. HOWEVER, 10 DAYS OF TREATMENT WITH HYPERCIUM
EXTRACT RESULTED IN A DECREASE OF DIGOXIN AUC(0-24) BY 25% (DAY 15, 17.2 + 4.0 UG. H/L AND 12.9 + 2.3 UG.H/L; P=.0035). FURTHERMORE, COMPARISON WITH THE PARALLEL PLACEBO GROUP AFTER MULTIPLE DOSING SHOWED A REDUCTION IN TROUGH CONCENTRATIONS
AND CMAX OF 33% (P=.0023) AND 26% (P-.0095), RESPECTIVELY. THE EFFECT BECAME INCREASINGLY PRONONUNCED UNTIL THE TENTH DAY OF CO-MEDICATION. AS WITH GRAPEFRUIT JUICE, A FOOD PRODUCT, PHYSICIANS SHOULD ALSO BE AWARE OF POTENTIAL DRUG-HERB
INTERACTIONS. THE INTERACTION OF ST JOHN'S WORT EXTACT WITH DIGOXIN KINETICS WAS TIME DEPENDENT. THE MECHANISM INVOLVED MAY BE INDUCTION OF THE P-GLYCOPROTEIN DRUG TRANSPORTER. |