Pharmacokinetic/pharmacodynamic integration of amphenmulin: a novel pleuromutilin derivative against Mycoplasma gallisepticum

Amphenmulin is a novel pleuromutilin derivative with great anti-mycoplasma potential. The present study evaluated the action characteristics of amphenmulin against Mycoplasma gallisepticum using pharmacokinetic/pharmacodynamic (PK/PD) modeling approaches. Following intravenous administration, amphenmulin exhibited an elimination half-life of 2.13 h and an apparent volume of distribution of 3.64 L/kg in healthy broiler chickens, demonstrating PK profiles of extensive distribution and rapid elimination. The minimum inhibitory concentration (MIC) of amphenmulin against M. gallisepticum was determined to be 0.0039 mu g/mL using the broth microdilution method, and the analysis of the static time-kill curves through the sigmoid E-max model showed a highly correlated relationship (R >= 0.9649) between the kill rate and drug concentrations (1-64 MIC). A one-compartment open model with first-order elimination was implemented to simulate the in vivo anti-mycoplasma effect of amphenmulin, and it was found that bactericidal levels were reached with continuous administration for 3 days at doses exceeding 0.8 mu g/mL. Furthermore, the area under the concentration-time curve divided by MIC (AUC/MIC) correlated well with the anti-mycoplasma effect of amphenmulin within 24 h after each administration, with a target value of 904.05 h for predicting a reduction of M. gallisepticum by 1 Log(10)CFU/mL. These investigations broadened the antibacterial spectrum of amphenmulin and revealed its characteristics of action against M. gallisepticum, providing a theoretical basis for further clinical development.