The combination of pyronaridine and artesunate is an antimalarial therapy in development. This mass balance study is intended to determine the rate and extent of excretion of total radioactivity in urine and feces following administration of a single oral micro-dose of 14C-pyronaridine in humans.
This is a monocenter, open-label, non-placebo-controlled, single-group, single-dose study. Six male subjects will receive a single dose of Pyronaridine 720 mg orally administered together with 14C-Pyronaridine (approx. 100 µg, 800 nCi (29600 Bq)). Safety measurements (12-lead ECG, vital signs, blood chemistry and haematology) and adverse events will be monitored throughout the study. Subjects will come to the clinic the evening before the dosing of Pyronaridine. After the drug intake at day 1, subjects will have regular in-house periods for specimen collection up to 87 days after the drug administration. Blood, feces and urine will be collected during the hospitalisation periods. Samples will be analyzed for radioactivity by Accelerator Mass Spectrometry (AMS).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Single dose of 720 mg Pyronaridine together with 14C-Pyronaridine (approx. 100 µg, 800 nCi).
Covance Clinical Research Unit AG
Allschwil, Basel, Switzerland
Analysis of 14C-Pyronaridine Total Radioactivity in Urine
Radioactivity recovery in urine as a percent of the administered dose. Continuous collection of samples was performed through 168 hours post-dose, with intermittent 48 hour collections occurring thereafter
Time frame: 2064 hours
Analysis of 14C-Pyronaridine Total Radioactivity in Feces
Radioactivity recovery in feces as a percent of the administered dose. Continuous collection of samples was performed through 168 hours post-dose, with intermittent 48 hour collections occurring thereafter
Time frame: 2064 hours
Total Radioactivity in Blood: AUC0-t, AUC0-∞
Pharmacokinetic Parameters: AUC0-t: area under the plasma concentration-time curve from Hour 0 through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was collected AUC0-∞: area under the plasma concentration-time curve from Hour 0 to infinity PK sampling performed at predose, 0.5, 1, 2, 4, 8, 12 and 24 hours, and 2, 4, 6, 7, 14, 21, 28, 35 and 42 days post-dose
Time frame: 42 days
Total Radioactivity in Blood: Cmax
Pharmacokinetic Parameters: Cmax: maximum observed peak observed concentration PK sampling performed at predose, 0.5, 1, 2, 4, 8, 12 and 24 hours, and 2, 4, 6, 7, 14, 21, 28, 35 and 42 days post-dose
Time frame: 42 days
Total Radioactivity in Blood: Half-life, Tmax
Pharmacokinetic Parameters: Half-life: computed as ln (2) / Kel Tmax: time to maximum concentration PK sampling performed at predose, 0.5, 1, 2, 4, 8, 12 and 24 hours, and 2, 4, 6, 7, 14, 21, 28, 35 and 42 days post-dose
Time frame: 42 days
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