Your browser doesn't support javascript.
loading
Population Pharmacokinetics of Linezolid in Tuberculosis Patients: Dosing Regimen Simulation and Target Attainment Analysis.
Alghamdi, Wael A; Al-Shaer, Mohammad H; An, Guohua; Alsultan, Abdullah; Kipiani, Maia; Barbakadze, Ketevan; Mikiashvili, Lali; Ashkin, David; Griffith, David E; Cegielski, J Peter; Kempker, Russell R; Peloquin, Charles A.
Afiliação
  • Alghamdi WA; Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
  • Al-Shaer MH; Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
  • An G; Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA.
  • Alsultan A; Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
  • Kipiani M; National Center for TB and Lung Diseases, Tbilisi, Georgia.
  • Barbakadze K; National Center for TB and Lung Diseases, Tbilisi, Georgia.
  • Mikiashvili L; National Center for TB and Lung Diseases, Tbilisi, Georgia.
  • Ashkin D; TB Control Section, Division of Disease Control and Health Protection, Florida Department of Health, Tallahassee, Florida, USA.
  • Griffith DE; Department of Medicine, University of Texas Health Sciences Center, Tyler, Texas, USA.
  • Cegielski JP; University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
  • Kempker RR; Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia, USA.
  • Peloquin CA; Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USA peloquin@cop.ufl.edu.
Antimicrob Agents Chemother ; 64(10)2020 09 21.
Article em En | MEDLINE | ID: mdl-32778547
The prolonged treatment duration for multidrug-resistant tuberculosis (MDR-TB) makes linezolid dosing difficult because of adverse effects associated with long-term use. We sought to find the optimal dosing regimen for linezolid across different MIC values. Pharmacokinetic (PK) data from TB patients were included from Brazil, Georgia, and two U.S. sites. Population PK modeling and simulation were performed. We used an fAUC (area under the unbound drug concentration-time curve)/MIC ratio of >119 as the PK/pharmacodynamic (PD) target and minimum (trough) concentrations of drug (Cmins) of 2 and 7 mg/liter as thresholds for toxicity. The PK/PD breakpoint was defined as the highest MIC at which the probability of target attainment is >90%. A total of 104 patients with pulmonary TB were included, with a median age and weight of 37 years and 60 kg. Eighty-one percent had drug-resistant TB. The PK data were best described by a one-compartment model. The PK/PD breakpoint was 0.125 mg/liter for a total daily dose of 300 mg, while daily doses of 450 to 600 mg and 900 to 1,200 mg had PK/PD breakpoints of 0.25 and 0.50 mg/liter, respectively. The probability of achieving a Cmin of ≤2 mg/liter was higher when the dose was given at once than when dividing it into 2 doses. Linezolid at a daily dose of 300 mg may not be optimal. We predicted an excellent and comparable efficacy of linezolid using total daily doses of 900 and 1,200 mg for MICs of ≤0.5 mg/liter but with the potential for more toxicity than with 600 mg daily. The increase in Cmin was noticeable when the daily dose was divided and may incur greater toxicity.
Assuntos
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Tuberculose Resistente a Múltiplos Medicamentos Tipo de estudo: Health_economic_evaluation / Prognostic_studies Limite: Humans País/Região como assunto: America do norte / America do sul / Brasil Idioma: En Revista: Antimicrob Agents Chemother Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Arábia Saudita País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Tuberculose Resistente a Múltiplos Medicamentos Tipo de estudo: Health_economic_evaluation / Prognostic_studies Limite: Humans País/Região como assunto: America do norte / America do sul / Brasil Idioma: En Revista: Antimicrob Agents Chemother Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Arábia Saudita País de publicação: Estados Unidos