tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2020 Apr 20. pii: AAC.00119-20. doi: 10.1128/AAC.00119-20. [Epub ahead of print]
Population Pharmacokinetics and Exposure-Response Relationships of Baloxavir Marboxil in Patients Infected with Influenza at High Risk of Influenza Complications.
Koshimichi H[SUP]1[/SUP], Retout S[SUP]2[/SUP], Cosson V[SUP]2[/SUP], Duval V[SUP]3[/SUP], De Buck S[SUP]2[/SUP], Tsuda Y[SUP]4[/SUP], Ishibashi T[SUP]4[/SUP], Wajima T[SUP]4[/SUP].
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Abstract
Baloxavir marboxil, a prodrug of cap-dependent endonuclease inhibitor, baloxavir acid, reduces the time to improvement of influenza symptoms in patients infected with type A or B influenza virus. To characterize its pharmacokinetics, a population pharmacokinetic model for baloxavir acid was developed using 11846 plasma concentration data items from 1827 subjects including 2341 plasma concentration data items from 664 patients at high risk of influenza complications. A three-compartment model with first-order elimination and first-order absorption with lag time well described the plasma concentration data. Body weight and race were found to be the most important factors influencing clearance and volume of distribution. The exposures in high-risk patients were similar to those in otherwise healthy patients, and no pharmacokinetic difference was identified regarding any risk factors for influenza complications.Exposure-response analyses were performed regarding the time to improvement of symptoms and the reduction in the influenza virus titer in high-risk patients. The analyses suggested that body weight-based dosage, 40 mg for patients weighing < 80 kg and 80 mg for patients weighing ≥ 80 kg, can shorten the time to improvement of influenza symptoms and reduce virus titer for both type A and B influenza virus regardless of the exposure levels of the high-risk patients as well as for the otherwise healthy influenza patients.The results of our population pharmacokinetic and exposure-response analyses in patients with risk factors of influenza complications should provide useful information on the pharmacokinetic and pharmacodynamic characteristics of baloxavir marboxil and also for the optimization of dose regimens.
Copyright ? 2020 Koshimichi et al.
PMID:32312784DOI:10.1128/AAC.00119-20
Free full text
Population Pharmacokinetics and Exposure-Response Relationships of Baloxavir Marboxil in Patients Infected with Influenza at High Risk of Influenza Complications.
Koshimichi H[SUP]1[/SUP], Retout S[SUP]2[/SUP], Cosson V[SUP]2[/SUP], Duval V[SUP]3[/SUP], De Buck S[SUP]2[/SUP], Tsuda Y[SUP]4[/SUP], Ishibashi T[SUP]4[/SUP], Wajima T[SUP]4[/SUP].
Author information
Abstract
Baloxavir marboxil, a prodrug of cap-dependent endonuclease inhibitor, baloxavir acid, reduces the time to improvement of influenza symptoms in patients infected with type A or B influenza virus. To characterize its pharmacokinetics, a population pharmacokinetic model for baloxavir acid was developed using 11846 plasma concentration data items from 1827 subjects including 2341 plasma concentration data items from 664 patients at high risk of influenza complications. A three-compartment model with first-order elimination and first-order absorption with lag time well described the plasma concentration data. Body weight and race were found to be the most important factors influencing clearance and volume of distribution. The exposures in high-risk patients were similar to those in otherwise healthy patients, and no pharmacokinetic difference was identified regarding any risk factors for influenza complications.Exposure-response analyses were performed regarding the time to improvement of symptoms and the reduction in the influenza virus titer in high-risk patients. The analyses suggested that body weight-based dosage, 40 mg for patients weighing < 80 kg and 80 mg for patients weighing ≥ 80 kg, can shorten the time to improvement of influenza symptoms and reduce virus titer for both type A and B influenza virus regardless of the exposure levels of the high-risk patients as well as for the otherwise healthy influenza patients.The results of our population pharmacokinetic and exposure-response analyses in patients with risk factors of influenza complications should provide useful information on the pharmacokinetic and pharmacodynamic characteristics of baloxavir marboxil and also for the optimization of dose regimens.
Copyright ? 2020 Koshimichi et al.
PMID:32312784DOI:10.1128/AAC.00119-20
Free full text