| Disease | THE PRESENT STUDY COMPARED JAPANESE DATA AGAINST THE PHARMACOKINETIC CHARACTERISTICS OF GLYCYRRHIZIN AFTER SINGLE AND MULTIPLE INTRAVENOUS DOSES IN 35 EUROPEAN PATIENTS WITH CHRONIC HEPATITIS C INFECTION. WE ADMINISTERED 80, 160, OR 240 MG
GLYCYRRHIZIN 3 TIMES/WK OR 200 MG GLYCYRRHIZIN 6 TIMES/WK FOR 4 WEEKS. 24-HOUR PHARMACOKIETIC ASSESSMENTS WERE PERFORMED ON DAY 1 AND ON OR AROUND DAY 14. GLYCYRRHIZIN LEVELS WERE DETERMINED BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY. THE MEAN
(+/-SD) VOLUME OF DISTRIBUTION AT STEADY STATE ON DAY 1 IN THE 80-, 160-, AND 240-MG GROUPS WERE 67+/- 11.62, 13,54+/- 7, AND 66+/- 8 ML/KG, RESPECTIVELY. THE RESPECTIVE TERMINAL ELIMINATION HALF-LIVES ON DAY 1 WERE 7.7+/- 2.8 10.1+/- 1.4, 9.0
+/- 2.3 AND 8.6+/- 2.1 HOURS. THE AREA UNDER THE CURVE (AUC) INCREASED LINEARLY WITH DOSES <200MG (R =0.67; P<0.001). NO SIGNIFICANT DIFFERENCES BETWEEN DAY 1 AND DAY 14 WERE FOUND IN ANY DOSE GROUP, WITH THE EXCEPTION OF AUC IN THE 200-MG
GROUP, WHICH WAS SIGNIFICANTLY HIGHER ON DAY 14 COMPARED WITH DAY 1 (P=0.03). COMPARING THE EUROPEAN AND JAPANESE DATA, THE MEAN (+/-SD)AUC WAS 289 +/- 244 MICRO/H PER ML FOR THE FORMER AND 402+/- 372 MICRO/H PER ML FOR THE LATTER; THE HALF-
LIFE WAS 8.2+/- 2.6 VERSUS 8.8+/- 9.0 HOURS; AND THE TOTAL CLEARANCE WAS 7.6+/- 3.6 VERSUS 8.5+/- 5.7 ML/H PER KG. THUS OUR PHARMACOKINETIC DATA ARE COMPARABLE TO THOSE FROM JAPAN. GLYCYRRHIZIN'S PHARMACOKINETICS ARE LINEAR UP TO 200 MG. DRUG
ACCUMULATION IS SEEN AFTER 2 WEEKS OF TREATMENT WITH 200 MG ADMINISTERED 6 TIMES/WK. |