1986 Volume 39 Issue 9 Pages 2436-2449
Pharmacokinetic and clinical studies were carried out regarding the use of cefotiam (CTM) in the treatment of infections in newborn infants.
1. Absorption and excretion
CTM was administered by bolus intravenous injection at a dose of 20mg/kg to 9 newborns ranging in age from 1 to 28 days (gestational age, 34-40 weeks; birth weight, 2,000-3,380g) and 6 infants aged 30 to 87 days (gestational age, 33-40 weeks; birth weight, 2,100-3,600g) and its serum concentration and urinary excretion were determined.
In the newborns, mean serum concentrations were 43.3μg/ml at 1/4 hour, 36.7μg/ml at 1/2 hour, 27.8μg/ml at 1 hour, 17.7μg/ml at 2 hours, 8.8μg/ml at 4 hours and 4.8μg/ml at 6 hours, and in the infants, they were 44.5μg/ml, 31.2μg/ml, 19.1μg/ml, 7.6μg/ml, 2.2μg/ml and 0.7μg/ml at the above sampling times, respectively.
Mean half-lives were 1.92 hours for the newborns and 0.96 hour for the infants, and mean urinary recoveries within 6 hours were 41.2% and 50.1% for the newborns and the infants, respectively.
Taking individual differences into account, serum peak levels (at 1/4 hour) in newborns were very similar to each other irrespective of age (days after birth), and did not appear to be greatly different from those in infants. Half-lives, however, became shorter with aging, and the half-life of the serum CTM level in infants of about 1 month old should be close to those in young children or school-age children.
From these observations, it is suggested to establish a standard regimen in which CTM is administered at a dose of 20mg/kg once or twice a day to newborns within 3 days after birth, twice or 3 times a day to those aged 4 to 7 days, and 3 or 4 times a day to those aged 8 days or older.
2. Clinical study The CTM was administered to 11 patients with acute pneumonia, 2 patients each with suspected septicemia and with bullous impetigo, 1 patient with purulent lymphadenitis, 3 patients with idiopathic respiratory distress syndrome and 1 patient with pneumothorax, and its clinical effect was investigated.
Excellent responses were observed in 12 of the 15 evaluated cases, good responses in 2, and a poor response in 1, thus an overall clinical effectiveness was 93.3%. Regarding the bacteriological response, 1 of 2 strains of S. aureus disappeared but the other persisted. One strain of E. coli was eliminated and 2 strains of K. pneumoniae reduced. Thus, the elimination rate was 40.0%.
No side effects were found clinically in any of the cases. As to abnormal laboratory values, elevations of GOT and GPT were noted in 3 cases, elevation of GOT in 2 cases, and eosinophilia in 1 case. These changes were slight and were normalized in all the cases except 2 in which a retest or a follow-up could not be conducted.
The above results suggest that CTM is useful and safe in the treatment of infections in newborns.
