PHARMACOKINETICS AND CLINICAL STUDIES ON FLOMOXEF IN NEONATES AND PREMATURE INFANTS

We investigated pharmacokinetics and clinical effects of flomoxef sodium (6315-S, FMOX) in neonates and premature infants.<BR>These results are summarized as follows:<BR>1. Pharmacokinetics<BR>(1) Plasma concentration (Ct) and half-lives (T 1/2) were determined upon after intravenous one-shot injection (i. v.) of FMOX to neonates of different day-age groups (0-3 (n=25), 4-7 (n=18), 8-28 (n=32) days of birth).<BR>At a dose of 10mg/kg. i. v., mean C₃₀(30 minutes concentration) values were 21.2, 21.8 and 21.3μg/ml, respectively, in the different groups mentioned above, and the mean T 1/2 values were 3.37, 1.85 and 1.63 hours. At 20mg/kg i. v., mean C₁₅(15 minutes concentration) values were 54.4, 51.4 and 50.7μg/ml, and mean T 1/2's were 2.99, 2.32 and 1.79 hours, respectively. At a dose of 40mg/kg i. v., mean C₁₅ values were 104.0, 95.9 and 99.2μg/ml, and the mean T 1/2's were 3.40, 1.20 and 1.80 hours, respectively.<BR>(2) Plasma concentrations and T 1/2 after intravenous one-shot injection of FMOX in premature infants in group (0-3 (n=14), 4-7 (n=10), 8-28 (n=13) days of birth).<BR>Mean C₁₅'s at doses of 10, 20 and 40mg/kg in the different groups of infants were 24.0, 28.6, 21.7 and 54.0, 54.6, 55.5 and 98.2, 93.0, 106.0μg/ml, and T 1/2's were 4.10, 2.53, 2.57 and 4.28, 2.27, 3.02 and 4.66, 2.86, 2.09 hours, respectively.<BR>Mean Cmax values were clearly dose dependent, and mean T 1/2 values tended to be longer in premature infants compared to neonates.(3) Urinary recovery rate of FMOX after intravenous injection in neonates and premature infants.<BR>Mean urinary recovery rates of FMOX in the first 6 hours after i. v.(one-shot) at doses of 10, 20 and 40mg/kg to neonates and premature infants were 38.9-62.8% in the neonates and 30.7-61.5% in the premature infants.<BR>(4) Plasma concentrations and urinary recovery rates upon 1 hour drip infusion of 20mg/kg in the neonate groups (or the premature infant groups) as follows: Mean C₅₀ values were 31.0, 32.7 and 23.4μg/ml, and T 1/2 were 2.94, 3.68 and 2.25 hours, respectively.<BR>The recovery rates were 35.2-52.9% in the first 6 hours after administration.<BR>2. Clinical studies<BR>The number of clinically evaluable cases in the FMOX treatment of premature infants was 199, in which the causative pathogens were indentified in 71 cases (A group) and not indentified in 128 cases (B group).<BR>Diseases among the A group were sepsis in 13 cases, purulent meningitis in 1, pneumonia in 18, other respiratory tract infections (RTI) in 3, urinary tract infection (UTI) in 13, skin and soft-tissue infection (SSTI) in 20, intrauterine infection in 2 and other infection in 1.<BR>The clinical efficacies in the A group was excellent in 40 cases, good in 27, fair in 1 and poor in 3. The over-all efficacy rate was 94.4%.<BR>Diseases in the B group included suspected sepsis in 24 cases, purulent meningitis in 1, pneumonia in 42, bronchitis in 2, other RTI in 2, UTI in 2, SSTI in 7, intrauterine infection in 44 and other infections in 4.<BR>The clinical efficacies in the B group were excellent in 54 cases, good in 69 and fair in 2. The over-all efficacy rate was 96.1%.<BR>FMOX was administered to 104 patients for prophylaxis with satisfactory results were obtained in all cases.<BR>3. Bacteriological studies<BR>Seventy three strains of pathogens were isolated from 71 cases. Bacteriological effects of FMOX were as follows, eradicated; 62 strains, decreased; 1, unchanged; 2, unknown; 7 and 1 strain was replaced. The bacteriological eradication rate was 95.5%.<BR>4. Side effects and abnormal laboratory test results were found at rates of 1.3% and 8.5%, respectively. However, all of these cases were transient and no severe incidents were observed.