Early Human Trial Maps How Defibrotide Clears From the Blood

Noseda and colleagues, writing in Haemostasis in 1986, tracked how quickly the body clears defibrotide, a polydeoxyribonucleotide extract with blood-thinning properties, after it is injected into the bloodstream.

The study was a small human pharmacokinetics trial, the kind of early-phase work that measures how a drug moves through and leaves the body rather than whether it treats disease. Five healthy volunteers received a single rapid intravenous injection at one of three doses — 0.5, 4 or 16 mg per kilogram of body weight. Two more volunteers received a 200-mg bolus followed by a slow six-hour infusion of 600 mg. Blood levels were measured using a method, supplied by the company Crinos, that detects a breakdown product called 6-desoxyribose.

The drug's half-life — the time for blood levels to fall by half — lengthened with dose: 9.8 minutes at the lowest dose, 14.2 minutes at the middle dose, and 21.1 minutes at the highest, suggesting the body's clearance system becomes saturated at higher amounts. During the slow infusion, blood levels stabilized at 10-15 micrograms per milliliter after 90-120 minutes. The study involved only seven people total and did not examine effectiveness, safety outcomes, or longer-term dosing.