title: Open-label, dose escalation study of the safety and pharmacokinetic profile of tefibazumab in healthy volunteers.
abstract: Tefibazumab (Aurexis) is a humanized monoclonal antibody being evaluated as adjunctive therapy for the treatment of Staphylococcus aureus infections. This open-label, dose escalation study evaluated the safety and pharmacokinetics of tefibazumab in 19 healthy volunteers aged 18 to 69 years. Each subject received a single administration of tefibazumab at a dose of 2, 5, 10, or 20 mg/kg of body weight infused over 15 min. Plasma samples for pharmacokinetic assessments were obtained before infusion as well as 1, 6, 12, and 24 h and 3, 4, 7, 21, 28, 42, and 56 days after dosing. Plasma concentrations of tefibazumab were detected 1 h after the end of the infusion, with a mean maximum concentration of drug in serum (C(max)) of 59, 127, 252, and 492 microg/ml following doses of 2, 5, 10, and 20 mg/kg, respectively. The median time to maximum concentration of drug in serum (T(max)) was 1.0 h for each dose. The mean elimination half-life (t(1/2)) was approximately 22 days. The volume of distribution (V) was 4.7, 6.7, 7.2, and 7.2 liters after doses of 2, 5, 10, and 20 mg/kg, respectively. Clearance (CL) was 6.0, 9.2, 10.2, and 9.9 ml/hr, respectively. At the highest dose, plasma levels of tefibazumab were >100 microg/ml for 21 days. On day 56, the mean plasma concentrations were 6.3, 10.0, 16.4, and 30.5 microg/ml for the 2, 5, 10, and 20 mg/kg doses, respectively. Tefibazumab exhibited linear kinetics across doses of 5, 10, and 20 mg/kg. No anti-tefibazumab antibodies were detected after dosing in any subject. There were no serious adverse events, and tefibazumab was well tolerated over the entire dose range.
authors.affiliation: Northwest Kinetics, Tacoma, Washington, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Reilley
authors.forename: Eric
authors.initials: E
authors.lastname: Wenzel
authors.forename: Laurie
authors.initials: L
authors.lastname: Reynolds
authors.forename: Beth
authors.initials: B
authors.lastname: Bennett
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Patti
authors.forename: Seth
authors.initials: S
authors.lastname: Hetherington
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000493:pharmacokinetics; D019540:Area Under Curve; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000628:therapy*
chemical_list: D018829:Adhesins, Bacterial; D000911:Antibodies, Monoclonal; C434058:clfB protein, Staphylococcus aureus
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