SIMULTANEOUS IN VITRO SIMULATION OF MULTIPLE ANTIMICROBIAL AGENTS WITH DIFFERENT ELIMINATION HALF-LIVES IN A PRE-CLINICAL INFECTION MODEL.
Comput Chem Eng
; 1552021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34924641
ABSTRACT
Combination therapy for treatment of multi-drug resistant bacterial infections is becoming common. In vitro testing of drug combinations under realistic pharmacokinetic conditions is needed before a corresponding combination is eventually put into clinical use. The current standard for design of such in vitro simulations for drugs with different half-lives is heuristic and limited to two drugs. To address that void, we develop a rigorous design method suitable for an arbitrary number of N drugs with different half-lives. The method developed offers substantial flexibility and produces novel designs even for two drugs. Explicit design equations are rigorously developed and are suitable for immediate use by experimenters. These equations were used in experimental verification using a combination of three antibiotics with distinctly different half-lives. In addition to antibiotics, the method is applicable to any anti-infective or anti-cancer drugs with distinct elimination pharmacokinetics.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Idioma:
En
Revista:
Comput Chem Eng
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos