Open AccessHuman Pharmacokinetics of BL-P1654 Compared with Ampicillin
Author(s) -
J. T. Clarke,
Robert Libke,
Edward D. Ralph,
Ruedi Lüthy,
William M. M. Kirby
Publication year - 1974
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.6.6.729
Subject(s) - probenecid , ampicillin , pharmacokinetics , volume of distribution , half life , penicillin , intramuscular injection , antibiotics , urine , medicine , pharmacology , chemistry , biochemistry
BL-P1654 is a new ureido-penicillin which has significant activity against both pseudomonas and klebsiella. Its pharmacokinetics were evaluated in five studies in four healthy adult male volunteers after 1-g doses given as: 5- and 30-min intravenous infusions, a 30-min infusion 1 h after the oral administration of 1 g of probenecid, and an intramuscular injection. For comparison, volunteers also received a 30-min infusion of 1 g of ampicillin. Serum levels of the antibiotic were found to fit a two-compartment open model using a Burroughs-5500 computer. After a 30-min infusion, peak serum levels of BL-P1654 (72.8 μg/ml [standard deviation] ± 5.9) were 50% greater than those of ampicillin (53.6 ± 8.9). Six hours later, the relative difference was even greater (4.58 ± 0.25 versus 0.35 ± 0.09). At 75 min after the 1-g intramuscular injection of BL-P1654, peak serum levels averaged 28.4 ± 10.3 μg/ml. The half-life of BL-P1654 (2.04 h) was significantly longer than for ampicillin (1.15 h), and the renal clearances of BL-P1654 and ampicillin were 79 versus 244 ml/min per 1.73 m2 , respectively. Probenecid produced no significant change in blood levels, volume of distribution, half-life, or renal clearance, indicating that there is no net tubular secretion of this antibiotic.