Effect Of Angelica Decoction On The Pharmacokineties Of Ketoconazole In Healthy Volunteer

OBJECTIVESTo assess the effect of Angelica decoction on the pharmacokinetics of ketoconazole in healthy volunteers.METHODS1. Dose administrationA randomized open, two-period crossover, single center trial own control human trials were assigned.5 subjects consecutive Angelica decoction,5 subjects received placebo for 7 days 10 healthy subjects were given Angelica decoction of 7 consecutive days before a single oral dose of ketoconazole 200 mg. Each visit was separated by at least a one-week washout period to allow for the elimination of ketoconazole to avoid treatment-by-period interactions.2. Biology samples collection and analysisBlood samples were collected from an in-dwelling venous at 0,0.33, 0.67,1,1.5,2,3,4,6,8,12 and 24h before and aftere ketoconazole administration. Blood samples were collected in plastic containers, and immediately centrifuged. The separated plasma samples were immediately frozen at-70℃until assayed.Concentrations of ketoconazole were determined in plasma by HPLC.3 Adverse reaction monitoringAll adverse reactions were recorded in the two-period crossover human trials. Blood pressure, body temperature, heart rate, ECG and other indicators were recorded 1h,2h,3h and 4h after ketoconazole administration.RESULTS1. Determination of ketoconazole The calibration curve were linear in the range of 025-9.9μg·mL-1 for ketoconazole.The limit of detection (LOD) were 0.25μg·mL-1. The extraction recoveries for ketoconazole were above 86.58%. The methodology recoveries were 97.54%～102.54%. The intra-day and inter-day RSD were less than 5.62%.2. The effect of Angelica decoction on the pharmacokinetics of ketoconazoleAfter a week of taking Angelica decoction? compared with the control group, oral Angelica decoction decreased the AUC0-24h of ketoconazole by 24.75% and Cmax was ecreased by 21.63%, the CL/F and was increased by 52.87% and 31.09%, respectively. The clinical significance was considerable though there was no significant difference of these values among the two phases.3. Adverse effect assessmentNo clinically significant effects were observed after administration of Angelica decoction and ketoconazole.CONCLUSIONSAngelica decoction administration for 7 days increased the clearance of ketoconazole, decreased AUC and Cmax of ketoconazole.