| Disease | THE STUDY WAS CARRIED OUT IN TEN HEALTHY VOLUNTEERS USING A RANDOMISED CROSS-OVER DESIGN. SUBJECTS WERE STUDIED ON THREE OCCASIONS. WITH A WASHOUT PEROID OF 2 WEEKS. DURING EACH PEROID. SUBJECTS RECEIVED A PRETREATMENT OF 20O ML ORANGE JUICE
(CONTROL). FULL-STRENGTH GRAPEFRUIT JUICE OR HALF-STRENGTH GRAPEFRUIT JUICE TWICE DAILY FOR 5 DAYS. ON DAY 6, THE SUBJECTS WERE GIVEN A SINGLE ORAL DOSE OF 600 MG QUININE SULPHATE WITH 200 ML OF ONE OF THE JUICES. PLASMA AND URINE SAMPLES FOR
MEASUREMENT OF QUININE AND ITS MAJOR METABOLITE. 3-HYDROXYQUININE, WERE COLLECTED OVER A 48-HOUR PEROID AND ANALYSED BY MEANS OF A HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD. THE INTAKE OF GRAPEFRUIT JUICE DID NOT SIGNIFICANTLY ALTER THE
ORAL PHARMACOKINETICS OF QUININE. THERE WERE NO SIGNIFICANT DIFFERENCES AMONG THE THREE TREATMENT PEROIDS WITH REGARD TO PHARMACOKINETIC PARAMETERS OF QUININE, INCLUDING THE PEAK PLASMA DRUG CONCENTRATION (CMAX), THE TIME TO REACH CMAX (TMAX),
THE TERMINAL ELIMINATION HALF-LIFE (T1/2), THE AREA UNDER THE CONCENTRATION-TIME CURVE AND THE APPARENT ORAL CLEARANCE. THE PHARMACOKINETICS OF THE 3-HYDROXYQUININE METABOLITE WERE SLIGHTLY CHANGED WHEN VOLUNTEERS RECEIVED GRAPEFRUIT JUICE. THE
MEAN CMAX OF THE METABOLITE (0.25 +/- 0.09 MG 1-1, MEAN +/- SD) WHILE SUJBECTS RECEIVED FULL-STRENGHT GRAPEFRUIT JUICE WAS SIGNIFICANTLY LESS THAN DURING THE CONTROL PEROID (0.31 +/- 0.06 MG 1-1, P <0.05) AND DURING THE THE INTAKE OF HALF-
STRENGTH GRAPEFRUIT JUICE (0.31 +/- 0.07 MG L-1,P<0.05). CONCLUSION: THESE RESULTS SUGGEST THAT THERE IS NO SIGNIFICANT INTERACTION BETWEEN THE PARENT COMPOUND QUININE AND GRAPEFRUIT JUICE. SO IT IS NOT NECESSARY TO ADVISE PATIENTS AGAINST
INGESTING GRAPEFRUIT JUICE AT THE SAME TIME THAT THEY TAKE QUININE. SINCE QUININE IS A LOW CLEARANCE DRUG WITH A RELATIVELY HIGH ORAL BIOAVAILABILITY, AND IS PRIMARLY METABOLISED BY HUMAN LIVER CYP3A4, THE LACK OF EFFECT OF GRAPEFRUIT JUICE ON
QUININE PHARMACOKINETICS SUPPORTS THE VIEW THAT THE SITE OF CYP INHIBITION BY GRAPEFRUIT JUICE IS MAINLY IN THE GUT. |