Cefazolin and moxalactam pharmacokinetics after simultaneous intravenous infusion

Abstract

A high-performance liquid chromatographic method for the measurement of moxalactam concentrations in serum was modified to permit the simultaneous measurement of both moxalactam and cefazolin. We then studied whether the simultaneous administration of both moxalactam and cefazolin to nornal subjects would produce profiles of serum concentration versus time which were the same as those obtained after the administration of each drug individually. Six healthy adults received a 30-minfusion of cefazolin (10 mg/kg), followed in 2 days by the same dose of moxalactam. After 2 days, both antibiotics were administered together. A two-compartment model was found to adequately characterize the data, and the serum concentration curve for each drug when given alone was statistically identical to that obtained after simultaneous administration. Cefazolin was found to produce a significantly greater peak serum concentration (105 ± 14 versus 81 ± 21 ug/ml) and a significantly greater area under the curve (218 ± 42 versus 157 ± 19 lig.h/ml). The terminal half-life of moxalactam was not significantly longer than for cefazolin (2.2 ± 0.6 versus 2.0 ± 0.6 h, respectively). The method of simultaneous administration may have distinct advantages over conventional methods for studies of comparative tissue penetration.Studies which compare the penetration of two antibiotics into human tissue are often conducted in patients undergoing elective surgery, e.g., total hip replacement for bone penetration studies (7) or coronary vein bypass surgery for heart muscle penetration studies (4). The antibiotics are usually asigned randomly and are administered prophylactically before removal of the surgical specimen. The concentrations of the two drugs in tissue are then determined and compared. We describe here a method of simultaneous measurement and administration of moxalactam and cefazolin to normal volunteers which would appear to be adaptable to tissue penetration studies and which may have significant advantages over the conventional twogroup design. MATERIALS AND METHODSSubjects and drug administration. Six normal volunteers, three males and three females, ranging from 22 to 35 years in age and 51 to 84 kg in weight, participated in this study, with informed consent. Subjects were instructed to refrain from strenuous physical activity or alcohol ingestion during each study period. An indwelling heparin lock for infusion was placed in each volunteer on study day 1. Blood samples were also obtained from the heparin lock (after disposal of the first milliliter) except for the first and final samples, which were obtained by direct venipuncture.A 30-min infusion of 10 mg of cefazolin sodium per kg, dissolved in 50 ml of normal saline, was administered via an IVAC 530 constant-infusion pump (IVAC Corp., La Jolla, Calif.). At day 2 after the administration of cefazolin, each subject received a 30-min infusion of 10 mg of moxalactam disodium per kg, followed in 2 days by a simultaneous 30-min infusion of the same dose (as above) of both moxalactam...

Penetration of moxalactam and cefazolin into atrial appendage after simultaneous intramuscular or intravenous administration

“…The advantages of simultaneous administration of two antimicrobial agents for comparative studies of their tissue penetration have been identified recently (8). Half as many subjects are required for the same number of datum points (tissue concentrations), pairing of all data permits the use of more powerful statistical tests, many complicating factors are eliminated (e.g., differences in time of removal of tissue), concentrations of both drugs can be measured simultaneously if high-performance liquid chromatographic assay is available, and an antibiotic with relatively poor activity against a specific pathogen (e.g., moxalactam versus Staphylococcus aureus [3]) can still be studied when given with a reliable prophylactic agent.…”

“…The concentrations of moxalactam and cefazolin in serum were determined simultaneously by a high-performance liquid chromatographic assay according to the method of Diven et al (2), modified as previously described (8).…”

“…We recently reported that the pharmacokinetics of moxalactam and cefazolin in normal adults are as distinctive after simultaneous intravenous infusion as they are after separate infusion, and we proposed that the method of simultaneous administration may have significant advantages for comparisons of the penetration of antibiotics into tissue (8). This study was designed to compare the atrial appendage penetration of moxalactam with that of cefazolin after simultaneous administration by either the intravenous (i.v.)…”

Pharmacokinetics of moxalactam in elderly subjects

“…The major differences in moxalactam pharmacokinetics seen in the elderly appear to be related to diminishing renal function and highly variable nonrenal elimination. Creatinine clearance can be used in estimating moxalactam doses in the elderly without significant renal impairment, but recommendations for the use of serum creatinine as an estimation of renal function or drug half-life are not valid in this population group.The pharmacokinetic properties of moxalactam, a 1-oxabeta-lactam antibiotic, have been studied in children (19,22,23), normal adults mostly under the age of 60 (7,11,15,21,24,26,28), and patients with renal disease (1-3, 12-14, 18, 29). Because moxalactam is primarily eliminated unchanged by the kidney, a decrease in renal function associated with disease or aging should lead to an alteration in the elimination of the drug.…”

“…The pharmacokinetic properties of moxalactam, a 1-oxabeta-lactam antibiotic, have been studied in children (19,22,23), normal adults mostly under the age of 60 (7,11,15,21,24,26,28), and patients with renal disease (1-3, 12-14, 18, 29). Because moxalactam is primarily eliminated unchanged by the kidney, a decrease in renal function associated with disease or aging should lead to an alteration in the elimination of the drug.…”