PIII-3Dose-escalating study to investigate safety, tolerability, and pharmacokinetics of lonicera japonica extract in healthy volunteers

Abstract

BACKGROUND Lonicera japonica (LJ) has been applied to treatment of inflammatory diseases in Oriental medicine. We studied safety, tolerability, and pharmacokinetics of rising, single and multiple intravenous doses of aqueous extract from LJ, SKLJI in healthy volunteers. METHODS A randomized, placebo-controlled, double blind, dose-escalation study after single and multiple dosing was conducted. Total 80 subjects (56 for single, 24 for multiple; total 13 times for 4 days) were enrolled. Blood and urine samples were collected and subjects were monitored closely for adverse events throughout the study. RESULTS Seven and 14 cases of adverse events suspected to be related with SKLJI were reported in the single dose and multiple doses, respectively. They were mild, transient and relieved without an intervention. In single dose, Tmax were 30 min for 30 min-duration infusion, 5 min for bolus injection, respectively. The elimination half-life was 1.4–1.6 h. Linear pharmacokinetic profiles in a dose-proportional manner were shown and interindividual variations were 15%-30% in high dose group. Pharmacokinetics of multiple doses was similar to that of single dose group. The accumulation index ranged from 0.93 to 1.08, and renal clearance was 5–12 L/h. CONCLUSIONS SKLJI was safe and well tolerated as a single dose and multiple doses up to 100 mg. It showed linear pharmacokinetics proportional to dose-escalation, short elimination half-life, little accumulation, and relatively small interindividual variations. Clinical Pharmacology & Therapeutics (2005) 79, P58–P58; doi: 10.1016/j.clpt.2005.12.211