Studies were carried out on the in vivo kinetics and clinical efficacy of latamoxef (LMOX) in neonates and premature infants. The results are summarized below. Serum concentration and T1/2 following ...intravenous injection of LMOX to neonates LMOX was intravenously administered to neonates as one shot doses of 10 mg/kg and 20 mg/kg. The serum concentration of LMOX showed a dose-response to the 10 and 20 mg/kg doses in each of the 0--3 day-old group, 4--7 day-old group and 8--28 day-old group. The T 1/2 values were as follows; for the 10 mg/kg dose, 5.17 hours in the 0--3 day-old group, 3.28 hours in the 4--7 day-old group and 2.79 hours in the 8--28 day-old group; for the 20 mg/kg dose, 5.58 hours in the 0--3 day-old group, 3.46 hours in the 4--7 day-old group and 3.14 hours in the 8--28 day-old group. Thus, it is seen that the half-life of both dosages decreased as the infants became older. Serum concentration and T 1/2 following intravenous injection of LMOX to premature infants Similar to the case of neonates described above, the concentration of LMOX in the serum of the premature infants showed a dose-response to the 10 mg/kg and 20 mg/kg dosages. The T 1/2 values for the 0--3, 4--7 day-old and 8--28 day-old groups were 7.54, 3.93 hours and 6.25 hours, respectively, for the 10 mg/kg dose, and 10.8, 4.05 hours and 3.23 hours, respectively, for the 20 mg/kg dose. Again, it is seen that the half-life of both dosages decreased as the age of the prematurely-born infants increased. Serum concentration and T1/2 following 1-hour intravenous drip infusion of LMOX to neonates LMOX was administered to neonates in doses of 10 mg/kg and 20 mg/kg, by i.v. drip infusion over a 1-hour period. With both dosages, the peak serum concentration of LMOX occurred at the time of completion of the infusion. The T1/2 values for the 0--3, 4--7 day-old and 8--28 day-old groups were 5.41, 3.68 hours and 1.92 hours, respectively, for the 10 mg/kg dose, and 5.31, 2.67 hours and 4.86 hours, respectively, for the 20 mg/kg dose. Urinary excretion of LMOX in neonates and premature infants. The percentage of the administered LMOX dose contained in the urine excreted during the 6-hour period following intravenous administration of LMOX to neonates and premature infants was determined.(ABSTRACT TRUNCATED AT 400 WORDS)
Studies were carried out on the in vivo kinetics and clinical efficacy of latamoxef (LMOX) in neonates and premature infants. The results are summarized below. 1. Serum concentration and T1/2 ...following intravenous injection of LMOX to neonates LMOX was intravenously administered to neonates as one shot doses of 10mg/kg and 20mg/kg. The serum concentration of LMOX showed a dose-response to the 10 and 20mg/kg doses in each of the 0-3 day-old group, 4-7 day-old group and 8-28 day-old group. The T1/2 values were as follows; for the 10mg/kg dose, 5.17 hours in the 0-3 day-old group, 3.28 hours in the 4-7 day-old group and 2.79 hours in the 8-28 day-old group; for the 20mg/kg dose, 5.58 hours in the 0-3 day-old group, 3.46 hours in the 4-7 day-old group and 3.14 hours in the 8-28 day-old group. Thus, it is seen that the half-life of both dosages decreased as the infants became older. 2. Serum concentration and T1/2 following intravenous injection of LMOX to premature infants Similar to the case of neonates described above, the concentration of LMOX in the serum of the premature infants showed a dose-response to the 10mg/kg and 20mg/kg dosages. The T1/2 values for the 0-3, 4-7 day-old and 8-28 day-old groups were 7.54, 3.93 hours and 6.25 hours, respectively, for the 10mg/kg dose, and 10.8, 4.05 hours and 3.23 hours, respectively, for the 20mg/kg dose. Again, it is seen that the half-life of both dosages decreased as the age of the prematurely-born infants increased. 3. Serum concentration and T1/2 following 1-hour intravenous drip infusion of LMOX to neonates LMOX was administered to neonates in doses of 10mg/kg and 20mg/kg, by i. v. drip infusion over a 1-hour period. With both dosages, the peak serum concentration of LMOX occurred at the time of completion of the infusion. The T1/2 values for the 0-3, 4-7 day-old and 8-28 day-old groups were 5.41, 3.68 hours and 1.92 hours, respectively, for the 10mg/kg dose, and 5.31, 2.67 hours and 4.86 hours, respectively, for the 20mg/kg dose. 4. Urinary excretion of LMOX in neonates and premature infants The percentage of the administered LMOX dose contained in the urine excreted during the 6-hour period following intravenous administration of LMOX to neonates and premature infants was determined. In the neonates, this percentage was 39.6% of the 10mg/kg dose and 49.0% of the 20mg/kg dose, while in the premature infants the excretion levels were 47.9% of the 10mg/kg dose and 42.4% of the 20mg/kg dose. 5. LMOX concentration in cerebrospinal fluid Six patients with purulent meningitis were intravenously administered LMOX in a dose of 50mg/kg, repeated 4-6 times per day (1 patient was administered 22.0mg/kg by i. v. drip infusion). The LMOX concentration in the cerebrospinal fluid (CSF) was determined to range from 6.29 to 49.9μg/ml, with a mean of 22.4 μg/ml, for the period of the first 8 days after dosing, and a range of 2.88 to 10.4μg/ml, with a mean of 7.8μg/ml, was found for the period from the 9th day onward after dosing. The transfer to the CSF was thus good. In addition, the ratio of LMOX concentration in CSF and serum was found to show a maximum of 89%, with a mean of 28.2%. 6. Clinical results The clinical efficacy of LMOX therapy was evaluated in a total of 111 patients, consisting of 84 neonates and 27 young infants of 29-to 60-day-old. With regard to the administered dosage, 151-300mg/kg/day was given to patients with purulent meningitis, while 41-150mg/kg/day was administered to patients with other infections. These dosages were divided into 2-4 doses per day, administered as one shot intravenous injections. (1) Clinical efficacy during neonatal period Of the 7 patients with purulent meningitis, the clinical efficacy was rated as “good” or “excellent” in 5 patients, for an efficacy rate of 71.4%.
