Comparison of ampicillin and hetacillin pharmacokinetics in man

The pharmacokinetics of oral and intravenous doses of ampicillin were studied when ampicillin was given directly and as its inactive precursor, hetacillin. The two compounds were assayed separately in plasma using an electrophoresis‐bioautography method. Plasma concentration and urinary excretion rates of ampicillin after direct intravenous injection and after hetacillin administration were computer fitted using a two‐compartment open model. Hetacillin hydrolyzed rapidly and completely to ampicillin with an in vito half‐life of 11 ± 2 min. in eight human subjects. No differences were found in the distribution rate and volume constants, elimination rates and clearance parameters, and urinary recovery of ampicillin when it was given either as intravenous ampicillin or intravenous hetacillin. The major effect of intravenous hetacillin is that early plasma, urine, and peripheral compartment levels of ampicillin resemble those from a rapid absorption process, with a peak plasma concentration found at about 0.5 hr. Limited bioavailability studies in eight fasting subjects showed 32% absorption from ampicillin capsules, while 38 and 42% absorption values from hetacillin capsules were found in four fasting and four nonfasting subjects, respectively. The primary rationale for clinical use of ampicillin precursors is, in general, the improvement of the limited intestinal absorption of the antibiotic as well as increasing the stability of ampicillin in aqueous solutions.