Dose linearity testing of intravenous cefpirome (HR 810), a novel cephalosporin derivate

After intravenous injection of single doses of 0.25, 0.5, 1.0, 1.5 and 2.0 g of cefpirome (HR 810) to 46 healthy male volunteers in an open manner, concentrations of unchanged drug were estimated at various times in serum and urine, over 24 h and 48 h, respectively. Cefpirome concentrations were determined using both high pressure liquid chromatography (HPLC) and a microbiological assay. The measurements obtained were compared by linear distribution independent regression, and were found to be equivalent. A linear relationship between dose and AUC00 (r = 0.96) for both HPLC and microbiological assay was demonstrated for the doses tested (0.25 g to 2.0 g). The biological half-life (t1/2,beta) was determined by fitting a two-compartment open model to the data: t1/2,beta was about 2 h (HPLC, median values) and was not relevantly dose dependent. A general twice daily dosing will be recommended for the treatment of infections. Clinically relevant high concentrations of unchanged cefpirome were detected in urine already after the lowest dose (0.25 g) for about 12 h, and after the highest dose (2.0 g) for at least 24 h. General tolerance was good, only slight temporary taste disturbances immediately after injection were claimed by one volunteer after both 0.5 g and 1.0 g doses and by four volunteers receiving 2.0 g of cefpirome; however, no counter-measures were needed.