Dosage adjustment for ceftazidime in patients with impaired renal function

Summary Ceftazidime has good antibacterial activity against many Gram-negative micro-organisms including Ps. aeruginosa.The aim of the present study was to calculate a dosage adjustment regimen for renal failure patients and to test it in a second group of patients. A study was made of the pharmacokinetics of ceftazidime 1 g given as a single bolus i.v. injection in 20 patients in an intensive care unit with varying degrees of renal function, including patients on regular haemodialysis. The serum half-life of elimination (t_1/2) varied from 1.6 to 45 h depending on renal function. During haemodialysis the mean t_1/2 was 4.7 h. A good correlation between the renal clearance of creatinine and ceftazidime was observed. In most patients protein binding was lower than previously observed. From the pharmacokinetic data, a dosage adjustment regimen for patients with renal insufficiency was calculated, which studies in 7 further patients showed to be effective.Abbreviations C_t serum concentration at time t - and slopes of the bi-exponential curve of the fast and the slow disposition (overall elimination) processes - A and B intercepts of the distribution slope and elimination slope extrapolated to the ordinate - t_1/2 serum half-life of elimination - k₁₂ distribution rate constant for transfer from the central to the peripheral compartment - k₂₁ distribution rate constant for transfer from the peripheral to the central compartment - k₁₃ elimination rate constant from the central compartment - k_N and elimination rate constants from the central compartment in normal and impaired renal function, respectively - AUC area under the serum concentration-time curve from zero to infinity - V_t total apparent volume of distribution (area method) - V₁ and V₂ distribution volumes in the central and the peripheral compartments, respectively - CL total body clearance of ceftazidime - CL_R renal clearance of ceftazidime - CL_CR renal clearance of creatinine - T and dosing intervals in normal and impaired renal function - (m) pe (mean) prediction error - rmspe root mean squared prediction error