Overview of acylureidopenicillin pharmacokinetics

The acylureidopenicillins which have been in man are azlocillin, mezlocillin, piperacillin, and furazlocillin (Bay k 4999). They exhibit dose dependent pharmacokinetics and accordingly upon increasing the doses have serum levels which are higher than the multiple of the dose, longer serum half-life (t1/2), and lower clearances (total serum clearance, renal clearance, and non-renal clearance). With doses of 1-2 g, t1/2 very between 0.7-1.1 h, and with 5.0 g 1.2-1.8 g. The elimination phase distribution volume corresponds to 10-30% of the body weight. The agents are excreted mainly through the kidneys. Referenced to the antibacterial activity of unchanged drugs, 50-80% of intravenous doses are eliminated in the urine. Only 25-35% of the dose of furazlocillin is excreted unchanged in the urine. The t1/2 is increased in reduced renal function, but mezlocillin is relatively little influenced by renal failure. With identical dose sizes, azlocillin appears to be subject to dose dependent pharmacokinetics to a higher degree than mezlocillin and piperacillin. Higher serum levels are also reached by azlocillin and the t1/2 of this agent is increased more in reduced renal failure than is the case for mezlocillin. The biliary levels of the acylureidopenicillins are high. A considerable biliary excretion occurs in reduced hepatic parenchymal function. The serum protein binding of these compounds decreases with higher concentrations varying between some 30% for 200 micrograms/ml and 50% for 2 micrograms/ml of azlocillin and mezlocillin, a mean of 16% for piperacillin in concentrations ranging from 20-300 micrograms/ml, and an average of 60% for furazlocillin. The acylureidopenicillins penetrate into tissues, cerebrospinal fluid and foetuses to produce therapeutic levels. The levels are rather low in bone tissue.