Population pharmacokinetics of isepamicin and dosing regimens using the Bayesian method in patients with serious infectious diseases

• Published in: CHEMOTHERAPY Vol. 42; no. 2; pp. 202 - 213
• Main Authors: Nagayama, Yoshiaki, Tanaka, Yoshio, Someya, Kazuhiko, Takao, Yoshihiro, Yamazaki, Akira, Shinozaki, Kimikazu, Takahashi, Satoru
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 1994; 公益社団法人 日本化学療法学会
• Subjects: isepamicin; TDM; ペイジアン法; 動態パラメータ; 投与設計法; 母集団薬物; 臨床薬物動態理論
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.42.202

The population pharmacokinetics of isepamicin (ISP) and dosing regimens using the Bayesian method were examined to establish safe and effective ISP treatment. The subjects were 48 patients. The dosage was adjusted on the basis of therapeutic drug monitoring (TDM). 418 serum ISP concentrations were measured by fluorescence polarization immunoassay and analyzed by NONMEM based on a one-compartment model. The relationship between mean ISP clearance (CL) and creatinine clearance (Ccr) (L/h/kg) was CL=0.0104+0.728 x Ccr. The mean distribution volume (Vd) was 0.433L/kg. The SD of CL and Vd were 0.0187L/h/kg and 0.169L/kg, respectively. The coefficient of variation (%) for intraindividual and residual variability was 26.8%. The Bayesian method using the population pharmacokinetic parameters showed excellent predictive performance on serum ISP concentrations. In clinical response, the effective rate was 50.9% in all patients and 58.6% in patients with hematological disorder. The serum creatinine level was elevated during 5 courses (9.1%) of ISP therapy (0.5 mg/dl or more). These results indicate that the Bayesian method can be applied to dosage regimens. It is important to make ISP dosage regimens based on TDM for patients with serious infectious disease.