Pharmacokinetics of 2′, 3′‐dideoxyadenosine and 2′, 3′‐dideoxyinosine in patients with severe human immunodeficiency virus infection

This article describes the pharmacokinetics of 2′,3′‐dideoxyadenosine (ddA) and 2′,3′‐dideoxyinosine (ddI) as determined during phase I clinical trials in patients with acquired immunodeficiency syndrome and acquired immunodeficiency syndrome–related complex. Drug levels were determined by HPLC in plasma, cerebrospinal fluid, and urine after administration of the drugs either intravenously or as an oral liquid given with antacid. ddA was metabolized rapidly and quantitatively to ddI to such an extent that ddA was undetectable in the plasma even during continuous intravenous administration of ddA. The plasma kinetics of ddI were generally monoexponential and were characterized by a half‐life of 38 minutes. This probably does not accurately reflect the kinetics of the active species of ddI, which appears to be 2′,3′‐dideoxyadenosine triphosphate, formed intracellularly. Oral bioavailability was 38% for oral liquid given with antacid. The total body clearance averaged 1.00 L/kg/hr, with a volume of distribution of 1.01 L/kg. Approximately 36% of the intravenous dose could be recovered unchanged in the urine. The level of ddI in the cerebrospinal fluid 1 hour after drug infusion averaged 21% of that of the simultaneous plasma level. It is concluded that ddI has pharmacokinetic properties that are amenable to its clinical use. Clinical Pharmacology and Therapeutics (1990) 47, 647–654; doi: 10.1038/clpt.1990.86