Moxalactam pharmacokinetics in children

Abstract

We measured the serum concentrations of moxalactam in 10 children receiving antibiotic prophylaxis for surgery and in 18 children treated for documented or suspected infections. Moxalactam was administered intravenously at a dose of 50 mg/kg every 8 h. After the first dose in 28 patients, mean moxalactam concentrations 5 min, 30 min, 2 h, and 8 h after infusion were 257, 177, 82.2, and 17.5 ,ug/ml, respectively. The mean half-life (T112) was 2.44 h (range: 0.55 to 7.96 h). The mean distribution volume (VD) was 0.30 liters per kg. No significant accumulation was observed with multiple doses. Prophylactic and therapeutic groups had similar serum levels, T112, and VD. The five infants less than 1 year of age had a lower mean 30-min level (P < 0.01), larger VD (P < 0.001) and longer T1/2 (P < 0.025) than the children older than 1 year. A dose of 50 mg/kg produced 30-min levels in excess of 64 ,ug/ml in all patients studied, but 8-h trough levels were below the minimal inhibitory concentration breakpoint of 16 ,g/ml in 32% of patients.Moxalactam is a broad-spectrum beta-lactam antibiotic which is gaining increasing use in the treatment of serious pediatric infections. Its activity against gram-negative bacteria, including Haemophilus influenzae (8), and its penetration into the cerebrospinal fluid (9, 10, 15, 17) make it a reasonable alternative for the treatment of some cases of meningitis. Its activity against Enterobacteriaceae (6,7,13,18) and anaerobes (3) makes it an appealing choice for the treatment of children with ruptured appendix and other intraabdominal infections.The pharmacology of moxalactam has been extensively studied in healthy adults and in adult patients with normal and impaired renal function (1,4,14,16). Since studies in children have been much more limited, we examined the pharmacology of moxalactam in healthy children receiving prophylaxis for abdominal surgery, mainly appendectomy, and in seriously ill children receiving therapy for acute infections. MATERILS AND METHODSChildren from birth to 16 years were eligible for entry into the study. Patients with a history of penicillin or cephalosporin allergy, a history of anaphylaxis to any drug, severe renal insufficiency, or life-threatening infection for which conventional therapy was available were not eligible. Written informed consent was obtained from parents or legal guardians in all cases.

Pharmacokinetics of Anti-Infective Agents in Paediatric Patients

“…Serum concentrations of latamoxef (moxalactam) in 2 studies appeared to decrease in a biexponential fashion after a single intravenous dose (Romagnoli et al 1982;Schaad et al 1981). Furthermore, Schaad et al (1981) fit the serum concentration-time curves to a 2-compartment open-system model.…”

“…Furthermore, Schaad et al (1981) fit the serum concentration-time curves to a 2-compartment open-system model. Romagnoli et al (1982) performed a I-compartmental analysis because insufficient data points were collected during the early distribution phase to undertake a 2-compartment analysis. Other investigators also demonstrated a monoexponential decline in latamoxef serum concentrations (Reed et al 1983).…”

“…The tY2~ was inversely correlated with chronological age, while plasma CL correlated directly with chronological and gestational age. When a I-compartment model was used to determine pharmacokinetic parameters, Vd of 0.33 L/kg, tYz~ of 1.6 and 3.02 hours, and CL of 101 and 99.7 mllmin (6.06 and 5.98 L/h) were reported after administration of the first 50 mg/kg intravenous dose oflatamoxef to children for surgical prophylaxis or the treatment of documented or suspected infection outside the central nervous system (Reed et al 1983;Romagnoli et al 1982). A direct correlation between CL and chronological age was also shown (Reed et al 1983;Romagnoli et al 1982).…”

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.…”