Pharmacokinetics of moxalactam in elderly subjects

Abstract

The pharmacokinetics of moxalactam were studied in 19 male volunteers 60 years of age or older with normal liver function tests and a creatinine clearance of 2 60 mlmin. Moxalactam was administered in single or multiple intravenous or intramuscular doses. Rapid and complete intramuscular bioavailability was demonstrated in a subgroup of the study population. The mean plasma half-life was 2.9 ± 0.8 h for intravenous doses and 3.5 ± 0.9 h for intramuscular doses. Average renal clearances of 0.04 liters/kg per h accounted for 74.0 ± 15.0% of total plasma clearance. Moxalactam plasma clearance showed a statistically significant (P < 0.01) correlation with measured and calculated creatinine clearance. 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. There is also a possibility that the volume of distribution may decrease with aging (9). This study was undertaken to characterize moxalactam pharmacokinetics in an elderly male population. Additionally, the drug was administered intravenously (IV) and intramuscularly (IM) in crossover fashion to a subgroup of the study population to characterize IM bioavailability. MATERIALS AND METHODSSubjects. Nineteen male volunteers between the ages of 60 and 74 years and weighing 51 to 108 kg (mean, 79 ± 19 kg) participated in the study. Informed consent was obtained from each subject. Inclusion in the study required normal liver function tests and a measured creatinine clearance of -60 ml/min. Creatinine clearance was determined by two or three 24-h urine collections. Subjects requiring systemic antimicrobial therapy were excluded.Design. Moxalactam was administered IV in 50 ml of 5% dextrose in water over 20 min in single doses of 250 or 500 mg and in multiple doses of 250 or 500 mg every 12 h for seven doses. Moxalactam was administered IM in single doses of 250 or 500 mg and in multiple doses of 250 or 500 mg every 12 h for seven doses. The IM doses were given in 2 ml (250-mg dose) or 3 ml (500-mg dose) of sterile water for injection. Those patients receiving both IV and IM moxalactam had a minimum of 48 h between drug courses.Venous blood samples for the assay of plasma concentrations of moxalactam were obtained at 0, 0.17, 0.5, 1, 2, 4, 8, 12, and 24 h after the completion of the sin...

Clinical Pharmacokinetics of the Third Generation Cephalosporins

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Antimicrobial Therapy for the Elderly Patient

“…Moxalactam pharmacokinetics in elderly subjects has been studied in 19 men aged 60–74 years 104 . The serum half‐life was slightly prolonged and drug clearance correlated with renal function; nonrenal elimination was highly variable.…”

Considerations in Dosage Selection for Third Generation Cephalosporins

“…Cephalosporin dosage regimens and serum half-lives (t'l2) in neonates, children and the elderly. Dosages listed do not reflect those for life-threatening infection or meningitis (data from Andritz et al 1984;Blouin et al 1989;Borin et al 1990;Faulkner et al 1988b;Hayton 1986;LeBel et al 1985;Meyers et al 1987Meyers et al , 1989Sugihara et al 1988 Nilsson-Ehle 1987; Meyers et al 1989;Montamat et al 1989). Pharmacokinetic studies of ceftazidime, ceftizoxime, and cefmenoxime conducted in elderly populations showed a doubling of tl/, by the age of 70, indicating the need for dosage reduction for these renally eliminated cephalosporins in this age group.…”