抗真菌类药物药理学及血药浓度监测进展李朋梅.ppt

抗真菌药的药理学及血药浓度监测进展 中日医院 药学部李朋梅 201805.13  抗真菌药物分类 Mechanism Drug class Cell membrane (14-c-demethylase inhibitors) isavuconazole 4 (ergosterol binding bitors/binders ualene monooxygenase ell wall 1.3-D-glucan synthesis 1,3Dg 1.3- Intracellula Pyrimidine analogues/ Griseofulvin complex ai s ths pot ativo n afat mecnag isos ff sistemdianst. Rha is az ents w a us using graying. Its ot the glucan synthase Amal Mayo Clin Proc.201186(8)805-817  抗真菌药物治疗成功的影响因素 Pharmacodynamic (PD) Underlying disease status Antifungal resistanc Drug interactions (antagonism)? Treatment toxicity Lack of fungicidalactivity? Diagnosis/Management Pharmacokinetic(PK) Drug interactions Inadequate drug concentrations Intercurrent infections Absorption Lack of infection source control Distribution Virulence factors(eg, toxins) Biofilm formation Curr Opin Infect Dis. 2011, 24(suppl 2): s14- $29  抗真菌药TDM的指南建议 of recommendatio Prophylaxis Treatment Toxicity recommendation strong evidence quality evidence quality moderate moderate recommendation rong against strong against strong against strong agains evidence quality moderate weak strong recommendation strong against strong against strong against evidence quality strong against ng against strong against Therapeutic drug monitoring(TDM)of antifungal agents: guidelin the british Society for Medical Mycology. J Antimicrob Chemother 2014; 69: 1162-1176  三唑类药动学特点 Parameter lations FO suspension 400 mg i.v. and pood 4 mgkg i.v. bd; 200 mg p.o. bi o mo bid Absolute bioavailability >909 8%6-47% independent of food and gastric (capsules dependent on food and (availability decreased by fat-rich (dose-dependent; availabi lity nc pH, in contrast to increased by fat-rch foods Elimination Renab>faecal: primarily in >renal; primarily a Renab>faecal; primarily as Faecab>renal: extensively in CYP3A4 CYP2C19:2C9 3A4 UGT1A4 CYP inhibition CYP2C9>3A4>2c19 YP3A4,2c19,>2C9 CYP3A