High performance liquid chromatographic determination and pharmacokinetic investigation of amino-penicillins and their metabolites in man.

Abstract

The metabolism and pharmacokinetics of amino-penicillins such as ampicillin (AB-PC), hetacillin (IPAB-PC), talampicillin (TA-PC), amoxycillin (AM-PC) and cyclacillin (AC-PC) in man were investigated. An ion-pair reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of parent penicillins and their metabolites in human urine. The time courses of urinary excretions of unchanged penicillins and metabolites (penicilloic acid (PA) and penamaldic acid (PM)) up to 8 h after oral administration were determined by using the HPLC method. The moment analysis of urinary excretion rate-time curves gave mean residence times and excretion amounts of the various species. The ratios of excreted amounts to dose (500 mg) at infinite time were estimated to be: AB-PC: 29.4% for unchanged AB-PC, 4.3% for AB-PA and 2.0% for AB-PM (total 35.6%); IPAB-PC: 51.8% for AB-PC, 8.7% for AB-PA and 3.9% for AB-PM (total 63.9%); TA-PC: 68.8% for AB-PC, 10.2% for AB-PA and 4.5% for AB-PM (total 83.5%); AM-PC: 58.9% for unchanged AM-PC, 15.6% for AM-PA and 6.9% for AM-PM (total 81.4%); and AC-PC: 76.6% for unchanged AC-PC and 13.4% for AC-PA (total 90.0%). AC-PC gave no detectable amount of penamaldic acid. The rate constants for absorption, metabolism and urinary excretion were estimated from the moments of the time course curves by using a 1-compartment open model. The pharmacokinetic features of amino-penicillins and the prodrugs, are compared and discussed.