title: Influenza viral load and peramivir kinetics after single administration and proposal of regimens for peramivir administration against resistant variants.
abstract: We estimated the efficacy of the current single administration of peramivir on the basis of peramivir pharmacokinetics in the upper respiratory tract (URT) and determined the predictive peramivir concentration-time curve to assess its efficacy against viruses with decreased susceptibility to neuraminidase inhibitors. Serum, nasal swab, or aspiration samples were collected from 28 patients treated with 10 mg/kg body weight peramivir. The sequential influenza viral RNA load and susceptibility after peramivir administration were measured using a quantitative real-time reverse transcription-PCR and neuraminidase inhibition assay. The peramivir concentrations in the serum and URT after a single administration at 10 mg/kg were measured, and the predictive blood and URT peramivir concentration-time curves were determined to assess various administration regimens against resistant variants. The peramivir concentration decreased to <0.1% of the maximum concentration of drug in serum (Cmax) at 24 h after administration. Rapid elimination of peramivir from the URT by 48 h after administration may contribute to an increase in the influenza A viral load after day 3 but not to a decrease in the influenza B viral load, despite the absence of a decrease in the susceptibility to peramivir. A longer maintenance of a high level of peramivir in the URT is expected by divided administration rather than once-daily administration. When no clinical improvement is observed in patients with normal susceptibility influenza A and B, peramivir readministration should be considered. In severe cases caused by resistant variants, better inhibitory effectiveness and less frequent adverse events are expected by divided administration rather than once-daily administration with an increased dosage.
authors.affiliation: Department of Pediatrics, Fukushima Medical University, Fukushima, Japan smasatoki@yahoo.co.jp.
authors.forename: Masatoki
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Pediatrics, Soma General Hospital, Soma, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Pediatrics, Ohara General Hospital, Fukushima, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Pediatrics, Hoshi General Hospital, Koriyama, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sakuma
authors.affiliation: Department of Pediatrics, Soma General Hospital, Soma, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Takeyama
authors.affiliation: Department of Pediatrics, Iwase Hospital, Sukagawa, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oda
authors.affiliation: Department of Pediatrics, South Aizu Hospital, Minami-aizu, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Hosoya
mesh_terms: D000146:Acids, Carbocyclic; D000293:Adolescent; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D003517:Cyclopentanes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D024882:Drug Resistance, Viral / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006146:Guanidines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant; D009980:Influenza A virus / Q000187:drug effects* / Q000378:metabolism; D009981:Influenza B virus / Q000187:drug effects* / Q000378:metabolism; D007251:Influenza, Human / Q000188:drug therapy*; D007700:Kinetics; D008297:Male; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D019562:Viral Load / Q000187:drug effects*; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D006146:Guanidines; D014764:Viral Proteins; D009439:Neuraminidase; C414210:peramivir