The development of appropriate dosage of anti-bacterial and anti-fungal agents based on pharmacokinetics and pharmacodynamics

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Abstract

An initial loading procedure has been recommended to enable teicoplanin to promptly reach an effective serum concentration for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). The mean trough concentrations were 13.2 mg/L for patients with eradication of MRSA. I showed that the administration of ≥36 mg/kg during the first 3 days was effective in promptly obtaining a trough concentration target of ≥13 mg/L for the initial treatment of MRSA infections. The major adverse effect associated with linezolid treatment is reversible myelosuppression, primarily thrombocytopenia. I demonstrated that the incidence of linezolid-induced thrombocytopenia was higher among patients with renal failure than in patients with normal renal function. A statistically significant (p<0.01) and strong correlation (r=0.933) was observed between linezolid and creatinine clearance. A negative correlation (r=-0.567) was also shown between linezolid clearance and blood urea nitrogen. Voriconazole trough plasma concentration has been reported to correlate with hepatotoxicity. Logistic regression analysis revealed that the therapeutic range for the voriconazole trough concentration should be 2–4 mg/L. Nonlinear pharmacokinetic analysis suggested that voriconazole therapy should be initiated with a dose of 7.2–8.9 mg/kg/day for CYP2C19 wild type and 4.4–6.5 mg/kg/day for the non-wild type in patients. Anaemia and thrombocytopenia are major side effects of liposomal amphotericin B. I demonstrated that the doses of liposomal amphotericin B estimated to cause side effects of a low red blood cell count, anaemia and thrombocytopenia with 50% probability are 4.0, 3.3 and 3.0 mg/kg/day, respectively.

Original languageEnglish
Pages (from-to)1171-1177
Number of pages7
JournalYakugaku Zasshi
Volume132
Issue number10
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • linezolid
  • liposomal amphotericin B
  • teicoplanin
  • voriconazole

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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