Bio-analytical methods for investigating the effect of age, body mass index and gender on the PK/PD ratio of antibiotics.

Abstract

The effectiveness of antibiotics (ABs) is governed by achieving the adequate pharmacokinetic (PK)/pharmacodynamics (PD) ratio. In this study, fast LC-MS/MS methods were developed and validated for the bioanalysis of cefaclor (CFC), ciprofloxacin (CFC), roxithomycin (RXM) and clindamycin (CLD). Chromatographic separation was performed on a C18 Zorbax-Eclipse Plus (3.5 μm, 100 × 4.6 mm) using isocratic elution. Detection was performed by positive electrospray ionization. The methods were applied for the assessment of PK parameters in volunteers (n = 101, 64 male and 37 female) and the effects of age, body mass index (BMI) and gender were investigated. Good linearity (r2 ≥ 0.99), accuracy (>86%), precision (CV% ≤ 11) and extraction recovery (>83%) were observed for CFC, CFX, RXM and CLD. Application to PK studies revealed that age and BMI affected the Thalf and the AUC of RXM and CLD (p < 0.023). Gender difference affected the critical PK parameters of the four ABs (Thalf (U = 18; P = 0.036) of CFC, the Cmax of CFX (U = 30; P = 0.017), the Thalf (U = 23; P = 0.009) and AUC (U = 26; P = 0.008) of RXM and CLD), respectively. These results highlight the significance of age and BMI variations for RXM and CLD dosing. Furthermore, it indicates that the gender difference may be considered when adjusting the AB dose.