A population pharmacokinetic model of telavancin, a lipoglycopeptide antibiotic, was developed and used to identify sources of interindividual variability. Data were obtained from healthy subjects (seven phase 1 studies), patients with complicated skin and skin structure infections (cSSSI; two phase 2 and two phase 3 studies), and patients with hospital-acquired pneumonia (HAP; two phase 3 studies). A two-compartment open model with zero-order input best fit the telavancin data from healthy individuals and patients with cSSSI or HAP. Telavancin clearance was highly correlated with renal function and, to a lesser extent, with body weight. Other covariates were related to at least one parameter in cSSSI (gender, bacterial eradication, and surgery) or HAP (age of >= 75 years) but did not markedly affect exposure. These analyses support current dosing recommendations for telavancin based on patient weight and renal function.
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Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo, BrazilUniv Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo, Brazil
Nardotto, Glauco H. B.
Lanchote, Vera L.
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Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo, BrazilUniv Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo, Brazil
Lanchote, Vera L.
Coelho, Eduardo B.
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Univ Sao Paulo, Fac Med Ribeirao Preto, Sao Paulo, BrazilUniv Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo, Brazil
Coelho, Eduardo B.
Della Pasqua, Oscar
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GlaxoSmithKline, Clin Pharmacol Modelling & Simulat, Uxbridge, Middx, England
UCL, Sch Life & Med Sci, Clin Pharmacol & Therapeut Grp, London, EnglandUniv Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo, Brazil
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Arizona State Univ W, Sch Med, Phoenix, AZ USA
Univ Illinois, Coll Pharm, Dept Pharm Practice, Chicago, IL USATheravance Inc, San Francisco, CA 94080 USA
Gotfried, Mark H.
Shaw, Jeng-Pyng
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Theravance Inc, San Francisco, CA 94080 USATheravance Inc, San Francisco, CA 94080 USA
Shaw, Jeng-Pyng
Benton, Bret M.
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Theravance Inc, San Francisco, CA 94080 USATheravance Inc, San Francisco, CA 94080 USA
Benton, Bret M.
Krause, Kevin M.
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Theravance Inc, San Francisco, CA 94080 USATheravance Inc, San Francisco, CA 94080 USA
Krause, Kevin M.
Goldberg, Michael R.
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Theravance Inc, San Francisco, CA 94080 USATheravance Inc, San Francisco, CA 94080 USA
Goldberg, Michael R.
Kitt, Michael M.
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Theravance Inc, San Francisco, CA 94080 USATheravance Inc, San Francisco, CA 94080 USA
Kitt, Michael M.
Barriere, Steven L.
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Theravance Inc, San Francisco, CA 94080 USATheravance Inc, San Francisco, CA 94080 USA