title: Phase 1B study of the pharmacokinetics and safety of posaconazole intravenous solution in patients at risk for invasive fungal disease.
abstract: This was a phase 1B, dose-ranging, multicenter, pharmacokinetics, and safety study of cyclodextrin-based posaconazole intravenous (i.v.) solution administered through a central line to subjects at high risk for invasive fungal disease (part 1 of a 2-part study [phase 1B/3]). Initially, the safety and tolerability of single-dose posaconazole i.v. 200 mg (n = 10) were compared with those of a placebo (n = 11). Subsequently, 2 doses were evaluated, posaconazole i.v. 200 mg once daily (q.d.) (n = 21) and 300 mg q.d. (n = 24). The subjects received twice-daily (b.i.d.) posaconazole i.v. on day 1, followed by 13 days of posaconazole i.v. q.d., then 14 days of posaconazole oral suspension 400 mg b.i.d. The steady-state (day 14) exposure target (average concentration [areas under concentration-time curve {AUCs}/24 h, average concentrations at steady state {Cavgs}], of ≥ 500 to ≤ 2,500 ng/ml in ≥ 90% of the subjects) was achieved by 94% of the subjects for 200 mg posaconazole q.d. and by 95% of subjects for 300 mg posaconazole q.d. The desired exposure target (mean steady-state Cavg, ∼ 1,200 ng/ml) was 1,180 ng/ml in the 200-mg dosing cohort and was exceeded in the 300-mg dosing cohort (1,430 ng/ml). Posaconazole i.v. was well tolerated. Posaconazole i.v. 300 mg q.d. was selected for the phase 3 study segment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01075984.).
authors.affiliation: University Hospital Gasthuisberg, Leuven, Belgium johan.maertens@uzleuven.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.affiliation: University Hospital, Cologne, Germany.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
authors.affiliation: Johannes Gutenberg University, Mainz, Germany.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ullmann
authors.affiliation: Julius-Maximilians-Universität Würzburg, Germany.
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Heinz
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
authors.forename: Gopal
authors.initials: G
authors.lastname: Krishna
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
authors.forename: Hernando
authors.initials: H
authors.lastname: Patino
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Caceres
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kartsonis
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
authors.forename: Hetty
authors.initials: H
authors.lastname: Waskin
authors.affiliation: Merck & Co., Inc., Whitehouse Station, New Jersey, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000378:metabolism*; D019999:Pharmaceutical Solutions; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D019999:Pharmaceutical Solutions; D014230:Triazoles; C101425:posaconazole
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