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A Phase I Multiple‐Dose Escalation Study Characterizing Pharmacokinetics and Safety of ABT‐578 in Healthy Subjects
Author(s) -
Karyekar Chetan S.,
Pradhan Rajendra S.,
Freeney Tony,
Ji Qin,
Edeki Timi,
Chiu Wenzi,
Awni Walid M.,
Locke Charles,
Schwartz Lewis B.,
Granneman Richard G.,
O'Dea Robert
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005278807
Subject(s) - pharmacokinetics , medicine , pharmacology , tolerability , urine , adverse effect
ABT‐578, a sirolimus analog, is being developed for administration from drug‐eluting stents to prevent postimplantation neointimal hyperplasia. The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of ABT‐578. Healthy subjects randomly received placebo or ABT‐578 (200, 400, or 800 μg) as daily intravenous infusions for 14 days. ABT‐578 blood pharmacokinetics and urine excretion on days 1 and 14 were determined. The effect of ABT‐578 on mitogen‐stimulated lymphocyte proliferation was assessed. ABT‐578 pharmacokinetics was described by a 3‐compartment open model. The mean CL, V ss , and t 1/2 ranges were 4.0 to 4.6 L/h, 92.5 to 118.0 L, and 24.7 to 31.0 hours, respectively. ABT‐578 pharmacokinetics was dose and time invariant. Approximately 0.1% of ABT‐578 was excreted in the urine. ABT‐578 was well tolerated, and no systemic changes were observed in the mitogen‐stimulated lymphocyte proliferation. ABT‐578 was shown to be safe over a wide range of systemic exposures.