Single oral dose escalation pharmacokinetics of pleconaril (VP 63843) capsules in adults.
Pleconaril is an orally active broad-spectrum antipicornaviral agent with excellent penetration into the central nervous system and nasal epithelium. The authors report the results of a randomized, placebo-controlled, dose escalation study of pleconaril oral capsules following single-dose administration 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 chromatography. Pleconaril disposition was best characterized using a two-compartment open-model with first-order absorption. Fifty-five subjects completed the study (31 +/- 10 years, 77.6 +/- 11 kg). The administration of pleconaril was well tolerated. There was no difference in tmax, lambda z, ka, t1/2elim, Cl/F, or Vdss/F among the various dose groups. A significant difference in both Cmax and AUC was observed between study groups; however, this difference became insignificant when the parameters were corrected for dose. Cmax and AUC were dose proportional between 50 and 1000 mg (r2 > 0.97 and 0.90, respectively). Pleconaril demonstrates a favorable safety and pharmacokinetic profile following single-dose administration.
Abdel-Rahman
S M
SM
Section of Pediatric Clinical Pharmacology and Experimental Therapeutics, Children's Mercy Hospital, Kansas City, Missouri 64108, USA.
Kearns
G L
GL
D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002214:Capsules; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004415:Dyspepsia / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010080:Oxazoles; D016037:Single-Blind Method
D000998:Antiviral Agents; D002214:Capsules; D010069:Oxadiazoles; D010080:Oxazoles; C115201:pleconaril