PHARMACOKINETICS AND CLINICAL STUDIES ON AZTREONAM IN NEONATES AND PREMATURE INFANTS (THE FIRST REPORT)

STUDY ON EFFECTIVENESS AND SAFETY IN MONO-THERAPY WITH AZTREONAM

Abstract

Pharmacokinetics and clinical study of aztreonam (AZT) in neonates and premature infants were conducted with the following results:
1. Pharmacokinetics
(1) Serum concentrations of AZT at 30 minutes after one-shot intravenous injection of 10 mg/kg and 20 mg/kg to neonates including premature infants were 20.6-26.6μg/ml and 38.5-46.4μg/ml, respectively, and decreased thereafter. A dose response was observed in the serum concentrations with administration of AZT 10 mg/kg and 20 mg/kg.
(2) Serum half-lives (T 1/2) tended to be shorter in both mature and premature infants as their day-ages increased and T 1/2 tended to be prolonged in premature infants compared with mature infants.
(3) Changes in serum concentration upon one-hour intravenous drip infusion of AZT 20 mg/kg were very similar to those upon one-shot intravenous injection.
(4) Urinary excretions in the first 6 hours after one-shot intravenous injection of AZT 10mg/kg or 20 mg/kg tended to increase in mature infants as they grew and showed excretion rate of 26.2-54.3% but those in premature infants did not show any specific tendency with rate of 17.5-45.1%. Urinary excretions upon intravenous drip-infusion showed a tendency very similar to those upon intravenous injection.
2. Clinical studies
(1) Clinically evaluable cases of AZT treatment were 88 cases (91 diseases), in which pathogenic organisms were identified in 56 cases (Group A), i.e., sepsis 9, purulent meningitis 2, pneumonia 8, urinary tract infection (UTI) 33 and others. Total efficacy rate was 98.2% including “excellent” (39), “good”(16) and “fair”(1). Number of cases in which pathogenic organisms were unknown (Group B) was 11, i.e., suspected sepsis (4), pneumonia (3) and intrauterine infection (4) and the efficacy rate was 100% with “excellent”(4) and “good” (7). Thus, both group A and B showed excellent results. AZT was also given to 24 cases for prophylaxis and all the cases showed prophylactic effect of AZT.
(2) Bacteriologically AZT was deemed effective in 53 cases out of 56 (Group A) with identified pathogens “eradicated”(51) and “unchanged”(2), thus the bacterial eradication rate was 96.2%.
(3) A minor degree of loose feces was observed in 1 (1.3%) of 80 cases as a side effect. Abnormal laboratory test values found were eosinophilia (3 cases), elevation of GOT and GPT (2), platelet-increase (1), elevation of GOT (1), and thrombocytopenia·elevation of GOT·GPT·LDH (1). Every one of these was of a minor degree and transient.
From the above pharmacokinetics and clinical results, standard dosage of AZT to neonates and premature infants should be in a unit dose of 20 mg/kg, twice daily to those with ages between 0 and 3 days, and 2 to 3 times daily to those with ages 4 days and above, by intravenous injection or intravenous drip infusion.