Safety, tolerability, and pharmacokinetics of intravenous oseltamivir: single- and multiple-dose phase I studies with healthy volunteers.
There is an unmet need for an intravenous (i.v.) neuraminidase inhibitor, particularly for patients with severe influenza who cannot take oral medication. Two phase I pharmacokinetic and safety studies of i.v. oseltamivir were carried out in healthy volunteers. The first was an open-label, randomized, four-period, two-sequence, single-dose trial of 100 mg, 200 mg, and 400 mg oseltamivir i.v. over 2 h and a 75-mg oral dose of oseltamivir. The second was a double-blind, placebo-controlled, parallel-group, multiple-dose study in which participants were randomized to 100 mg or 200 mg oseltamivir or placebo (normal saline) i.v. over 2 h every 12 h for 5 days. Exposure to the active metabolite oseltamivir carboxylate (OC) after dosing achieved with 100 mg oseltamivir administered i.v. over 2 h was comparable to that achieved with 75 mg administered orally. Single i.v. doses of oseltamivir up to 400 mg were well tolerated with no new safety signals. Multiple-dose data confirmed good tolerability of 100 mg and 200 mg oseltamivir and showed efficacious OC exposures with 100 mg i.v. over 2 h twice daily for 5 days. These results support further exploration of i.v. oseltamivir as an influenza treatment option for patients unable to take oral medication.
Hoffmann-La Roche, Inc., Nutley, New Jersey, USA.
Barbara J
BJ
Brennan
Brian
B
Davies
Georgina
G
Cirrincione-Dall
Peter N
PN
Morcos
Anna
A
Beryozkina
Colombe
C
Chappey
Pau
P
Aceves Baldó
Sian
S
Lennon-Chrimes
Craig R
CR
Rayner
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D010919:Placebos
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D010919:Placebos; D053139:Oseltamivir; C535162:oseltamivir carboxylate