Sm. Abdel-rahman et Gl. Kearns, Single oral dose escalation pharmacokinetics of pleconaril (VP 63843) capsules in adults, J CLIN PHAR, 39(6), 1999, pp. 613-618
Pleconaril is an orally active broad-spectrum antipicornaviral agent with e
xcellent penetration into the central nervous system and nasal epithelium.
The authors report the results of a randomized, placebo-controlled, dose es
calation study of pleconaril oral capsules following single-dose administra
tion of 50 to 1000 mg Fifty-six healthy adults (ages 19-55) participated in
the study. Each subject received a single dose of pleconaril oral capsule(
s) or an identically matched placebo. Blood samples (n = 19) were obtained
over 36 hours postdose, and pleconaril was quantified from plasma by gas ch
romatography. Pleconaril disposition was best characterized using a two-com
partment open-model with first-order absorption. Fifty-five subjects comple
ted the study (31 +/- 10 years, 77.6 +/- 11 kg). The administration of plec
onaril was well tolerated. There was no difference in t(max), lambda z, ka,
t(1/2elim), Cl/F or Vdss/F among the various dose groups. A significant di
fference in both C-max and AUC was observed between study groups; however,
this difference became insignificant when the parameters were corrected for
dose. C-max and AUC were dose proportional between 50 and 1000 mg (r(2) >
0.97 and 0.90, respectively). Pleconaril demonstrates a favorable safety an
d pharmacokinetic profile following single-dose administration. (C) 1999 th
e American College of Clinical Pharmacology.