Correlation of the Pharmacokinetic Parameters of Amikacin and Ceftazidime

Abstract

Ceftazidime and amikacin are often prescribed concomitantly to treat infections caused by Gram-negative bacteria. Their physicochemical properties are quite similar. Both drugs are highly soluble in water, have low plasma protein binding and are >95% excreted unchanged by the kidney via glomerular filtration. Their pharmacokinetic parameters are therefore expected to correlate. This study was performed to explore the correlation between the pharmacokinetic parameters of these two drugs. Patients at Phramongkutklao Hospital, Bangkok, Thailand, who met the inclusion criteria participated in the study. They all received ceftazidime and amikacin concomitantly to treat their infections. After steady-state conditions had been reached, two blood samples were collected during the elimination phase of both drugs. Plasma drug concentrations were analysed and the pharmacokinetic parameters of each drug were calculated. The pharmacokinetic parameters that were examined included total drug clearance (CL), the elimination rate constant (k(e)), the elimination half life (t(1/2)) and the volume of distribution (V(d)). The correlations of the pharmacokinetic parameters of amikacin and ceftazidime were determined using regression analysis. Regression analysis showed that the pharmacokinetic parameters of ceftazidime and amikacin were highly correlated. The correlation coefficients (r) of CL, k(e), t(1/2) and V(d) of the two drugs were 0.966, 0.943, 0.888 and 0.671, respectively. The correlation between amikacin clearance and ceftazidime clearance was higher than the correlation between either amikacin or ceftazidime clearance and creatinine clearance, for which the r values were 0.647 and 0.661, respectively. The pharmacokinetic parameters of ceftazidime and amikacin were highly correlated. Knowledge of the pharmacokinetic parameters of one of these drugs can be used to predict the pharmacokinetic parameters of the other drug.