Document 0969
 DOCN  M95A0969
 TI    Delivery of 2',3'-dideoxyinosine via intratracheal instillation (Meeting
       abstract).
 DT    9510
 AU    Gao X; Wientjes MG; Jurcisek JA; Au JL; College of Pharmacy, Ohio State
       Univ., Columbus, OH 43210
 SO    Proc Annu Meet Am Assoc Cancer Res; 36:A2408 1995. Unique Identifier :
       AIDSLINE ICDB/95610182
 AB    We have shown that the low and variable oral bioavailability (average of
       17%, range of 8-23%) of the anti-AIDS drug, 2',3'-dideoxyinosine (ddI),
       in rats is primarily due to its first-pass elimination in gastric acid
       and by intestinal flora. This study evaluated whether the intratracheal
       administration route provides an improved systemic bioavailability. A
       ddI dose (40 mg/kg in 200 ul) was instilled into the trachea in female
       Fisher rats and an intravenous tracer dose (9 ug/kg) of 3H-ddI was
       administered concomitantly to determine the drug clearance. ddI was
       rapidly absorbed from the lungs; the peak concentration, 17.1 +/- 6.6
       ug/ml (mean +/- SD), was reached at 3.4 +/- 2.5 min. The ddI clearance
       was 74.0 +/- 12.6 ml/min/kg, and the intratracheal bioavailability was
       62.8 +/- 6.1% (range 55.0-73.4%). The instillation of a dye solution
       intratracheally showed that a fraction of the dose spilled over to the
       gastrointestinal tract, which may have caused the less-than-complete
       bioavailability. These data indicate a higher and less variable
       bioavailability of ddI by the intratracheal than by the oral route,
       which may be further enhanced by using appropriate formulations that
       localize the entire dose in the lung.
 DE    Animal  Biological Availability  Didanosine/*ADMINISTRATION &
       DOSAGE/PHARMACOKINETICS  Female  Rats  Rats, Inbred F344  Trachea
       MEETING ABSTRACT

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