[Data averaging in pharmacokinetic analysis: the population pharmacokinetics of cephalothin and cefazolin]

Cephalothin and cefazolin pharmacokinetics was studied in cats after intravenous administration in doses of 20 and 75 mg/kg. The antibiotic serum concentrations were determined microbiologically. It was shown that the antibiotic pharmacokinetics within the above dose ranges was linear. The data on the antibiotic pharmacokinetics were described by bioexponential equations. Various methods for estimating population pharmacokinetic parameters were compared. Two approaches were used in estimating the population parameters: (1) averaging of individual concentrations followed by determining a single set of the parameters (naive pooled data approach) and (2) calculating of the parameters for an individual concentration/time set followed by the parameter averaging (two-stage approach). With the use of every approach the geometric mean of the parameters was calculated along with the arithmetic one. When the two-stage approach was used the population parameters were estimated with two procedures: averaging of the hybrid parameters (macroconstants) and averaging of the microconstants. Estimation of the population parameters as a geometric mean of the individual parameters, proved to be the most preferable approach.