Models describing metronidazole pharmacokinetics in relation to hemodynamics in turkeys

Linking haemodynamic (HD) and pharmacokinetic (PK) parameters provides much insight into interrelations between circulatory system and drug disposition. This effect is particularly pronounced in rapidly growing animals. Heart rate (HR), cardiac output (CO) and stroke volume (SV) are tightly linked with the animal's age and correlate with the increasing body weight (BW). The aim of this study was to establish and validate the relations between BW, HD and chosen PK parameters of metronidazole (MTZ) and its metabolite - hydroxymetronidazole (MTZ-OH) in growing turkeys. The study was carried out on broiler turkeys (BUT-9, n = 26). All individuals were subjected to single dose PK studies four times, that is when the mean BW in the group reached: 1.4 (group A); 2.7 (group B); 5.5 (group C); 10.7 kg (group D). Some PK parameters normalized with regard to HR were found to take constant values in all the age groups under investigation. CO ↔ 1/MRT, SV ↔ 1/MRT and SV ↔ MRT model was validated with regard to both metabolite and drug PK. This study proposed a model for the analysis of the relations HD ↔ BW and HD ↔ PK. Models developed in this study provide empirical evidence that HD affect the PK of MTZ and MTZ-OH in a different fashion.