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 t max , lz, ka, t 1/2elim , Cl/F, or Vdss/F among the various dose groups. A significant difference 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 and pharmacokinetic profile following single‐dose administration .