Pharmacokinetic and clinical studies of cefotiam in neonates and premature infants

Cefotiam (CTM) was given to 25 mature and premature infants, ranging in age from 0 to 24 days, who have various nearly-healed bacterial infections. CTM was administered at the dose of 10 mg/kg by intravenous injections or by 1-hour intravenous drip infusions, or at the dose of 20 mg/kg by intravenous injections. Only a small number of subjects being examined, they were divided by their aged day into 3 groups; 0-3 days old, 4-7 days old and 8-24 days old. We compared the time courses of changes in serum and urine levels of CTM in these groups. The clinical study was done with 8 male and 4 female infants ranging in age from 3 days to 4 months. One had septicemia, 4 had bronchopneumonia, 3 had urinary tract infection, 1 had colitis, 2 had abscess, and 1 had maxillary sinusitis. Changes in serum and urinary levels of CTM Changes in serum levels after 10 mg/kg intravenous injection. Peak serum CTM levels of all 3 groups were achieved at 30 minutes after administration; the levels were between 11.7 and 23.6 micrograms/ml; and differences were not significant. Serum levels then gradually decreased in all the groups to 0.5-7.0 micrograms/ml at 6 hours after administration. Half-lives of serum CTM levels tended to be shorter in older infants; means were 2.7, 2.2 and 1.3 hours for the 0-3 day-old, the 4-7 day-old and the 8-24 day-old respectively. Changes in serum levels of CTM after 10 mg/kg 1-hour intravenous drip infusion. The 0-3 day-old and the 4-7 day-old had peak serum CTM levels, ranging from 16.3 to 35.8 micrograms/ml, at the end of drip infusion. Half-lives of serum CTM levels tended to be shorter in older infants, with 3.2 hours for the 0-3 day-old and 2.0 hours for the 4-7 day-old groups. Changes in serum levels after 20 mg/kg intravenous injection. The 0-3 day-old and the 4-7 day-old had peak serum levels, ranging from 30.6 to 42.1 micrograms/ml, at 30 minutes after administration, then serum levels of CTM in either group showed a gradual decrease to 2.5-11.4 micrograms/ml at 6 hours after injection.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies of cefotiam in the perinatal period

Patients, who had undergone cesarean sections, and those who had experienced premature rupture of membranes, received cefotiam (CTM) and the clinical efficacy and the safety for mothers and fetuses were investigated. At the same time, pharmacokinetic analysis was done to study the maternal fetal transfer. Following results were observed. In cases of premature rupture of membranes, the maternal-fetal transfer ratio after intravenous administrations of CTM was 50.3% at a dosage of 1 g. Maternal and fetal serum concentrations of CTM were maintained higher levels than the MIC80 (0.78 micrograms/ml) against major pathogens excluding anaerobic of gynecologic-obstetric infections and were maintained up to 5.87 hours and 6.15 hours in mothers and fetuses, respectively. The CTM was administered once every 12 hours at a dosage of 1 g to 38 cases up to the 3rd or 4th day of puerperium after the rupture of membranes. Also, the CTM was administered up to times of delivery to another 20 cases, in one of which the fetus developed pneumonia. The maternal-fetal prophylactic effect was recognized in 98.3% (57/58) of cases. Forty-three cesarean section cases received CTM at a dosage level of 1 g by one-hour intravenous drip infusion in the following manner: after surgery to the 4th day, twice a day; from the 5th to the 7th day, once a day. Postoperative prophylactic effect against infection was achieved in all the cases. In 1 case, a slight transient elevation in the maternal GOT was observed. Neonatal jaundice with total bilirubin levels higher than 15.0 mg/dl was observed in 19 neonates (32.8%) in the group in which premature rupture of the membranes had occurred. However, the cause/effect relationship between CTM and the total bilirubin levels is unclear. The maternal-fetal transition of CTM was excellent, and the safety toward the fetus and neonate was high. When an antimicrobial activity and pharmacokinetics are considered, CTM will be a useful drug in the treatment of perinatal infections.     

Fundamental and clinical studies of cefotiam in neonates and premature infants

Single doses of cefotiam (CTM) by bolus injection of 20 mg/kg of CTM were given to 17 neonates and premature babies (11 prematures) and plasma and urine CTM levels as well as urinary recovery rates of CTM were determined. The CTM was also evaluated clinically with regard to therapeutic and protective effects, bacteriological efficacy as well as safety. A mean daily dose of 56.6 mg/kg of CTM was given intravenously in 2 to 4 divided doses for an average of 8 days to 11 neonates and prematures consisting of 1 case with pneumonia, 2 suspected septicemia, 3 urinary tract infections and 5 for prophylaxis against infections. (In the 6 babies evaluated for clinical effects, a mean dose of 59.8 mg/kg/day of CTM was given for an average 9 days). The findings of these studies are summarized below: The mean peak plasma level of 2 cases of 4-7 day-old neonates was 32.3 mcg/ml 5 minutes after injection. The mean AUC was 96.6 mcg X hr/ml, and the mean half-life was 2.12 hours. In 3 of the 4 neonates of 8-14 day-old group, the mean peak plasma level of 55.6 mcg/ml was obtained after 5 minutes. The mean AUC was 63.0 mcg X hr/ml and the mean half-life was 0.82 hour. Compared to the 4-7 day-old group, AUC was smaller and half-life was shorter in this group. In premature infants, plasma CTM levels were determined in 2, 1, 1, 5 and 2 cases of the 0-3, 4-7, 8-14, 15-21 and 22-28 day-old infants, respectively. In the 8-14 day-old group and one of 15-21 day-old group, peak plasma levels were obtained after 15 minutes. Peak plasma levels in the remaining groups, were attained after 5 minutes. Peak plasma levels in the 5 groups were 40.7, 48.4, 33.9, 38.1 and 45.3 mcg/ml, respectively. Mean or individual AUC's obtained after excluding markedly varying values from the respective groups were 122.0, 96.2, 65.2, 72.8 and 60.4 mcg X hr/ml, respectively. With the increasing age, the AUC tended to decrease. Mean or individual half-lives were 2.31, 1.47, 1.28, 1.41 and 0.96 hours, respectively, showing a tendency to decrease with increasing age. In 6 neonates, high urinary levels continued up to 6 hours after administration. Mean 6-hour urine recoveries in the 4-7 and 8-14 day-old groups were 16.6% and 43.0%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Basic and clinical studies of cefotiam in neonates and premature infants

The effect of cefotiam (CTM) on neonates and premature infants was examined in basic and clinical studies. Minimum inhibitory concentrations of CTM against 190 clinically isolated strains kept by this department were investigated. This drug was found to have a strong antibacterial effect against Escherichia coli, Klebsiella spp., Proteus mirabilis and Streptococcus agalactiae, Staphylococcus aureus and Staphylococcus epidermidis, although some strains were resistant. The CTM was given to 0-3, 4-7, and greater than or equal to 8 day-old premature infants and neonates by intravenous injection at the dose of 20 mg/kg, and we studied changes in serum CTM levels over time. Mean serum CTM levels were 62.3 micrograms/ml at 15 minutes and 16.4 micrograms/ml at 6 hours after the injection, with the half-life of 3.6 hours, for the 0-3 day-old premature infants. They were 38.5 micrograms/ml at 15 minutes and 10.1 micrograms/ml at 6 hours, with the half-life of 2.9 hours, for the 0-3 day-old neonates. Those levels were 22.5 micrograms/ml at 15 minutes and 2.9 micrograms/ml at 6 hours, with the half-life of 1.9 hours, for the 4-7 day-old neonates, and 51.8 micrograms/ml at 15 minutes and 1.0 micrograms/ml at 6 hours, with the half-life of 1.1 hours, for the greater than or equal to 8 day-old neonates. The CTM was given to 0-3 and greater than or equal to 8 day-old premature infants and neonates by 1-hour intravenous drip infusion at the dose of 20 mg/kg, and changes in serum CTM levels after the infusion were followed. The 0-3 day-old premature infant (there was only one subject) had a peak serum CTM level of 21.0 micrograms/ml 1 hour after the start of the infusion (that is, at the time of its completion), with the level decreased to 8.6 micrograms/ml at 7 hours and the half-life was 5.4 hours. The mean peak serum CTM level in 0-3 day-old neonates were 36.7 micrograms/ml at 1 hour, which decreased to a mean of 7.0 micrograms/ml at 7 hours; the half-life was 2.3 hours.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies of ceftriaxone in neonates

Pharmacokinetic and clinical studies on ceftriaxone (CTRX) in mature and premature neonates were carried out. The results are summarized as follows. The mean serum peak level of CTRX after intravenous administration at a single dose of 10 mg/kg in 4 to 13 day-old-neonates was 34.1 +/- 11.4 micrograms/ml at 30 minutes. The mean serum level at 12 hours after dosage was 11.1 +/- 2.1 micrograms/ml. The mean half-life time was 11.6 +/- 1.4 hours. Mean serum peak levels of CTRX after intravenous administration at a single dose of 20 mg/kg were 64.6 +/- 15.4 micrograms/ml in 1 to 3 day-old-neonates, 44.6 +/- 1.1 micrograms/ml in 5 day-old-neonates at 30 minutes. Mean serum levels at 12 hours after dosage in these two groups of neonates were 16.4 +/- 4.8 micrograms/ml and 12.4 +/- 2.5 micrograms/ml, respectively. Mean half-life times were 13.7 +/- 3.7 hours in 1 to 3 day-old-neonates and 10.2 +/- 1.3 hours in 5 day-old-neonates. CTRX was clinically effective in a case of urinary tract infection. No side effect was observed except an elevation of GOT.     

Pharmacokinetic and clinical studies on amikacin in neonates

Pharmacokinetic and clinical studies on amikacin (AMK) were performed in neonates and the results obtained are summarized as follows. 1. After intramuscular injection of single doses of AMK at 3 mg/kg, peak serum levels were 6.8 micrograms/ml in a 2-day-old neonate and 7.0 micrograms/ml in a 20-day-old neonate. Serum levels of AMK in the above 2 neonates at 8 hours after injection were 1.5 micrograms/ml and 1.4 micrograms/ml, respectively, and the half-life of AMK was 3.3 hours. After intramuscular injection of single doses of 4 mg/kg of AMK, the mean peak serum level was 8.1 +/- 1.1 micrograms/ml, and half-lives of AMK were 6.1 hours in a 1-day-old neonate and 4.0 hours in a 3-day-old neonate. The mean peak serum level of AMK reached at 1 hour after intramuscular administrations at single dose of 6 mg/kg was 10.5 +/- 0.5 micrograms/ml in a 3-day and a 4-day-old neonates. Serum levels at 8 hours after administrations were 3.1 micrograms/ml and 2.8 micrograms/ml, in the 3-day and the 4-day-old neonates, respectively. Half-lives of AMK in sera were 3.9 hours in the 3-day-old neonate and 3.5 hours in the 4-day-old neonate. 2. In three 2-day-old neonates, the mean peak serum level of AMK after an intravenous drip infusion for 30 minutes at single dose of 3 mg/kg was 10.0 +/- 1.1 micrograms/ml at the end of infusion and serum levels decreased to 2.3 +/- 0.6 micrograms/ml at 6.5 hours after infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic and clinical studies on aztreonam in neonates

Pharmacokinetic and clinical studies on aztreonam (AZT) in mature and premature neonates were carried out. The results are summarized as follows. The mean serum peak level of AZT after intravenous administration at a single dose of 20 mg/kg in 3 to 4 day-old-neonates was 36.6 +/- 2.39 micrograms/ml at 1 hour after dosage. The mean serum level at 6 hours after dosage was 13.5 +/- 2.03 micrograms/ml. The mean half-life time was 3.86 +/- 0.92 hours. The mean urinary excretion rate was 25.1 +/- 5.18% in the first 6 hours after intravenous administration. AZT was administered in 4 cases, but the effects could not be evaluated. No side effect was observed except an elevation of GOT.     

Pharmacokinetic and clinical studies of cefotiam during the perinatal period in pregnant women

Pharmacokinetic and clinical studies of cefotiam (CTM) were carried out in pregnant women. The results obtained are summarized below. The concentration of CTM in amniotic fluid increased gradually up to 14.7 micrograms/ml at 4.5 hours after administration and gradually declined thereafter. This amniotic fluid concentration was sufficiently higher than reported MIC90's of CTM against E. coli strains. Passages of CTM to embryo, fetus and fetal appendages were minimal. The passage of CTM to milk was minimal. The CTM was used in the treatment of 6 pregnant patients with pyelonephritis and unknown fever and 1 with puerperal pyelonephritis. Clinical responses were positive in 85.7% (6/7). The CTM was used 7 patients with rupture of the membrane and 2 patients with operation for the purpose of prophylaxis and it was effective in 77.8% (7/9). Neither noteworthy adverse reactions nor abnormal laboratory data in our patients or neonates were observed throughout the studies.     

Pharmacokinetic, bacteriological and clinical studies of ceftizoxime in neonates

Pharmacokinetic, bacteriological and clinical studies of ceftizoxime (CZX) were performed in neonates. 1. Serum concentrations and urinary excretion of CZX were investigated in 12 neonates ranging ages from 1 to 27 days (gestational age, 35-41 weeks; birth weight, 2,150-4,030 g) and 2 infants ranging ages from 55 to 57 days (gestational age, 39-40 weeks; birth weight, 2,320-2,650 g). Each of the subjects was given a single intravenous dose of 20 mg/kg by one shot. Serum concentrations of CZX in the neonates were 24.9-53.7 micrograms/ml at 1/4 hour after intravenous injection, with an average of 40.6 +/- 7.6 micrograms/ml. Serum half-lives of CZX were 1.32-4.75 hours and averaged 2.60 +/- 1.06 hours. Serum concentrations ranged from 2.01 to 14.6 micrograms/ml at 6 hours after injection with an average of 7.70 +/- 3.89 micrograms/ml. In the 2 infants, serum concentrations were 42.0 and 46.2 micrograms/ml at 1/4 hour (average: 44.1 +/- 3.0 micrograms/ml), and 2.91 and 5.04 micrograms/ml at 6 hours after injection (average: 3.98 +/- 1.51 micrograms/ml). Half-lives were 1.54 hours in 1 infant and 1.93 hours in the other (average: 1.74 +/- 0.28 hours). Furthermore, 6-hour urinary recovery rates were 28.5-71.7% (average: 49.3 +/- 12.8%) in the neonates and 42.1-55.5% (average: 48.8 +/- 9.5%) in the infants. The above results suggest that the following 3 points are accepted; 1) peak serum concentrations (at 1/4 hour) in neonates were similar to those in infants and older children irrespective of age (days after birth). 2) Serum half-lives of CZX in neonates shortly after birth were 4 or 5 times longer than those in older children, but decreased rapidly with the advance of day-ages. The half-life in neonates of 2 weeks of age or so became shorter to about twice the normal value in infants. Furthermore, half-lives of the drug in those at an age of the first half of infancy were similar to those in older children. 3) The urinary excretion rates tended to be somewhat low with neonates soon after birth, but became very similar to those in infants and older children at a relatively early stage.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies on cefmenoxime in neonates and infants

Pharmacokinetic and clinical studies on cefmenoxime (CMX) in neonates and infants were conducted. 1. CMX 20 mg/kg was administered by intravenous bolus injection to 6 neonates (with ages 2 to 20 days) and 5 infants (with ages 36 to 107 days) and its serum concentration and urinary excretion rates were determined. In the neonates, serum concentrations of CMX after intravenous administration reached peak levels of 48.2 to 90.7 micrograms/ml (mean 70.4 +/- 14.3 micrograms/ml) in 1/4 hour, then declined with half-lives of 1.27 to 5.19 hours (mean 2.28 +/- 1.56 hours), and were 3.6 to 16.9 micrograms/ml (mean 8.3 +/- 6.0 micrograms/ml) at 6 hours. In the infants, serum concentrations at 1/4 hour were 67.5 to 111.0 micrograms/ml (mean 95.5 +/- 18.0 micrograms/ml); half-lives were 0.64 to 0.94 hour (mean 0.81 +/- 0.13 hour); and the serum concentrations at 6 hours were 0.2 to 1.1 micrograms/ml (mean 0.7 +/- 0.4 micrograms/ml). Mean peak serum concentrations in the neonates tended to be lower than those in the infants, but higher than those in children. Regarding the age differences of serum concentrations due to age in the neonates, their peak levels tended to be lower in younger ones. Half-lives were shorter in older subjects and, in early infancy, approached values observed in children. Urinary recovery rates in the first 6 hours after intravenous administration ranged from 43.6 to 87.5% (mean 61.6 +/- 14.6%) in the neonates and from 52.1 to 90.8% (mean 78.0 +/- 15.1%) in the infants. Thus, recovery rates were high even in younger subjects and tended to be higher in older subjects. 2. CMX was administered to 27 neonates and 4 infants to investigate its clinical effect, bacteriological effect and side effects. Clinical efficacy ratings of the drug in 19 neonate cases that could be evaluated (1 with purulent meningitis, 2 with suspected septicemia, 1 with acute bronchitis, 12 with acute pneumonia, 1 with impetigo, 1 with periumbilical abscess and 1 with acute pyelonephritis) were "excellent" in 14 cases, "good" in 4, and "poor" in 1. The efficacy rate covering "excellent" and "good" was 94.7%. In 4 infants (2 with acute pneumonia, 1 with periumbilical abscess and 1 with acute pyelonephritis), "excellent" was obtained in 2 cases and "good" in 2 cases. Thus, all the cases showed "good" or higher ratings. Bacteriologically, 1 strain of Staphylococcus aureus and 3 strains of Escherichia coli in neonates were eradicated while, in infants, 1 strain of S. aureus persisted but 1 of E. coli was eradicated.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic, bacteriological and clinical studies on aztreonam in neonates

Pharmacokinetic, bacteriological and clinical studies on aztreonam (AZT) were performed in neonates. The results obtained are summarized as follows. 1. Plasma levels and urinary excretion of AZT were determined in 18 neonates with ages between 1 and 30 days (gestation periods were 36 to 40 weeks and birth weights were 1,890 to 4,300 g) and in 2 infants with 54 and 60 days of age (gestation periods were 36 and 40 weeks, and birth weights were 2,300 and 3,300 g, respectively) upon one-shot intravenous injection of AZT 10 mg/kg (7 cases) or 20 mg/kg (11 cases) to the 18 neonates and 20 mg/kg to the 2 infants. Ampicillin (ABPC) 25 mg/kg was simultaneously injected to 5 cases of the neonates given AZT 20 mg/kg by one-shot intravenous injection and plasma concentrations of ABPC in these 5 cases were also studied. Plasma concentrations in neonates at 0.5 hour after intravenous injection of AZT 10 mg/kg were 11.5 to 27.6 micrograms/ml (average 20.3 +/- 5.5 micrograms/ml) and decreased with half-lives of 2.72 to 5.70 hours (average 3.81 +/- 1.28 hours), and the plasma levels at 8 hours after administration were 3.3 to 8.7 micrograms/ml (average 5.8 +/- 2.5 micrograms/ml). In the cases given AZT at 20 mg/kg, plasma levels at 0.5 hour were 12.4 to 48.8 micrograms/ml (average 35.9 +/- 11.6 micrograms/ml) and decreased with half-lives of 1.69 to 4.14 hours (average 2.94 +/- 0.76 hours) and AZT levels at 8 hours were 1.1 to 10.6 micrograms/ml (average 5.6 +/- 3.6 micrograms/ml). Urinary recovery rates in the first 8 hours after intravenous injection of the 10 mg/kg group were 15.5 to 61.9% (average 37.8 +/- 21.8%) and 16.3 to 62.2% (average 43.5 +/- 16.2%) for the 20 mg/kg group. Plasma concentrations in infants after administration of AZT 20 mg/kg were 33.0 to 35.6 micrograms/ml (average 34.3 +/- 1.8 micrograms/ml) at 0.5 hour and decreased with half-lives of 1.76 to 3.77 hours (average 2.77 +/- 1.42 hours) and AZT plasma levels at 8 hours were 1.4 to 5.8 micrograms/ml (average 3.6 +/- 3.1 micrograms/ml). Urinary recovery rates were 35.4 to 64.8% (average 50.1 +/- 20.8%). These results suggested that AZT shows a dose-dependent, high plasma concentration even in the neonatal period, as well as good urinary excretion from an early stage of the administration.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies of cefmenoxime in neonates and premature infants

Serum concentrations and urinary recovery rates of cefmenoxime (CMX) were determined in 41 mature and premature infants (with ages 0-24 days) after one shot intravenous injection of 10, 20 (1-hour intravenous drip infusion was also carried out) or 30 mg/kg for treatment and prophylaxis of various infections. Because the number of cases included was small, a comparison study was conducted by classifying them into 3 groups; 3 days or younger, 4 to 7 days, and 8 days or older, rather than dividing them into groups of mature and premature infants. Clinical evaluation was conducted in 7 male and 1 female cases 1 to 29 days old, whose diseases comprised 1 case each with septicemia, purulent otitis media and phlegmonous cellulitis, 3 with pneumonia and 2 with urinary tract infection. 1. Changes in serum concentrations and urinary recovery rates (1) Intravenous bolus injection of 10 mg/kg: Serum concentrations of the drug in the 3 age groups peaked at 28.9, 29.5 and 29.1 micrograms/ml, respectively, all at 30 minutes after the drug administration, and thereafter gradually declined. The mean level in the 3rd group was the lowest at 1.9 micrograms/ml at 6 hours. Average serum half-lives of CMX were shorter in older subjects, 3.0, 1.9 and 1.4 hours, respectively in the 3 groups. Urinary recovery rates were relatively high, 68.9 to 84.9% in the 3 cases examined during the first 6 hours, and 15.4 to 66.2% during the first 2 hours. (2) Intravenous bolus injection of 20 mg/kg: Serum concentrations of the drug in the 3 groups peaked at 65.2, 60.5 and 65.8 micrograms/ml, respectively, all at 30 minutes after the drug administration, with no significant differences noted among the groups. The levels gradually declined thereafter in all groups, but remained rather high at 20.1, 6.5 and 9.5 micrograms/ml, respectively, at 6 hours. Average serum half-lives of CMX were 3.5, 1.7 and 1.9 hours, respectively. The inversion of values obtained between the 2nd and 3rd groups appears to be attributable to that all of the 3rd group were premature infants, and the body weight of 2 cases of them were less than 2,000 g each. Urinary recovery rates ranged widely from 37.0 to 89.4% in the 4 cases examined during the first 6 hours. (3) One-hour intravenous drip infusion of 20 mg/kg: Serum concentrations of the drug in the 3 groups peaked at 57.7, 60.2 and 72.4 micrograms/ml, respectively, all at the termination of the drug infusion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies on cefmenoxime in neonates and premature infants

Cefmenoxime (CMX) was administered by intravenous bolus injection to a total of 23 neonates and premature babies with aged 1 to 26 days at a dose of 10 or 20 mg/kg and their plasma and urine concentrations and urinary recovery rates were determined up to 6 hours after administration. In addition, for the treatment of bacterial infections, diagnosed or suspected, or for the prophylaxis of bacterial infections, the drug was administered to a total of 27 neonates, premature babies and infants, with ages of 0 day to 3 months. It was possible to evaluate therapeutic efficacy and prophylactic efficacy in 15 cases and 7 cases, respectively. In these cases, side effects and bacteriological effects and, in some of them, changes in laboratory test values were also investigated. The obtained results are summarized below. 1. At a dose level of 10 mg/kg (n = 7), peak plasma concentrations at 5 minutes after administration, were 42.6 microns/ml in neonates with ages of 15 to 21 days and 45.9 microns/ml in those with ages of 22 to 28 days in a group of less than 2,500 g b.w. (birth weight), and 36.9 microns/ml in neonates with ages of 4-7 days and 38.9 microns/ml in those of 8-14 days in the other group of greater than of equal to 2,500 g b.w., indicating no large differences among the 4 subgroups (each of the above concentration values is either the value for an individual when only one neonates was involved or a mean value when 2 or more neonates were involved. The same applies hereinafter). Though 1 exceptional case showed a biphasic change, its cause is unknown. Half-lives in the above-mentioned 4 subgroups were 1.5, 1.6, 2.4 and 1.9 hours, respectively. The half-life of 2.4 hours in 1 patient with an age of 5 days of the greater than or equal to 2,500 g b.w. group was longer than in any of the other 3 subgroups. 2. At 20 mg/kg (n = 16) dosage level, mean peak plasma concentrations were 63.8 microns/ml in the infants of 0-3 days, 68.1 microns/ml in those of 8-14 days and 59.4 microns/ml in those of 15-21 days in the group of less than 2,500 g b.w., and 109.9 microns/ml in the neonates aged 8-14 days and 79.7 microns/ml in those of 15-21 days in the group greater than or equal to 2,500 g b.w.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies on aztreonam in neonates and premature infants

Aztreonam (AZT) was studied for its pharmacokinetics, clinical effect and effect on intestinal bacterial flora in neonates, and the results obtained are summarized as follows: 1. Serum concentrations of AZT upon intravenous administration of 20 mg/kg were 38.6 micrograms/ml in 30 minutes, 30.6 micrograms/ml in 1 hour and 13.6 micrograms/ml in 6 hours. The T 1/2 was 3.73 hours. Ampicillin (ABPC) 25 mg/kg was concurrently used with AZT in 2 cases and serum concentrations of AZT in these 2 cases were 40.3 and 36.9 micrograms/ml in 30 minutes, 35.7 and 32.6 micrograms/ml in 1 hour, and 13.1 and 10.2 micrograms/ml in 6 hours, respectively. T 1/2's were 3.32 and 2.91 hours, respectively, and no interaction between the 2 drugs was observed. 2. AZT was administered to 21 neonates between 0 and 83 days of age and ABPC was concurrently administered to 18 of the cases. Clinical evaluation was made in 14 cases, where AZT was remarkably effective in 7 cases, effective in 6 cases and not effective in 1 case. Of the 21 cases, 1 case of diarrhea, 1 case each of eosinophilia, an increase in platelets, an increase in platelets and an elevation of GOT and a decrease in platelets were recorded. 3. With respect to effects of AZT on intestinal bacterial flora, fecal concentrations of AZT upon its single administration to 2 cases were low suggesting, there was little effect on the intestinal flora. Some effect on anaerobes, however, was recognized in 4 cases in which ABPC was concurrently used.     

Pharmacokinetic and clinical studies with imipenem/cilastatin sodium in neonates

Pharmacokinetic and clinical evaluations of imipenem/cilastatin sodium (IPM/CS) were carried out in neonates. The following results were obtained: 1. The plasma concentrations of IPM/CS were determined upon doses of 10 mg/10 mg/kg and 20 mg/20 mg/kg administered using 30- and 60-minute drip infusion, respectively. Peak concentrations of IPM/CS were 19.0-34.7 micrograms/ml/32.6-73.4 micrograms/ml, respectively, at the end of the drip infusion. Plasma half-lives of IPM and CS were 1.4-1.6 hours and 1.7-2.1 hours, respectively. 2. Over a period of 6-8.5 hours, urinary excretions of IPM and CS totaled 19.8-42.7% and 46.9-89.3% of the dose administered, respectively. 3. Clinical responses to IPM/CS were excellent in 4 patients, good in 8 patients and unknown in 1 patient. 4. No side effect was observed except for a platelet increase in 2 patients. From the above results, it has been concluded that IPM/CS is an effective and safe drug in the treatment of neonatal infections.     

Pharmacokinetic and clinical studies on flomoxef in mature and premature infant]

Pharmacokinetic and clinical studies of flomoxef (FMOX) in neonates and premature infants were conducted, and the results obtained are summarized below. 1. Plasma concentrations of FMOX at 15 minutes after one shot intravenous injection of 20 mg/kg to 6 cases were in a rang of 33.0-69.9 micrograms/ml and half-lives (T 1/2's) were between 0.68 and 4.89 hours. The plasma concentration of FMOX at 15 minutes after one shot intravenous injection of 40 mg/kg to 1 case was 79.9 micrograms/ml and the half-life (T 1/2) was 2.45 hours. Drug concentrations in plasma upon 1-hour intravenous drip infusion were 71.1-114.0 micrograms/ml and T 1/2's were 1.64-3.41 hours. T 1/2 tended to be couse shorter as ages of babies increased. 2. Urinary excretion rates in the first 6 hours after one shot intravenous injection of FMOX 20 mg/kg to 1 case and 1-hour intravenous drip infusion of FMOX 40 mg/kg to 2 cases were 60.4%, and 27.2 and 55.3%, respectively. 3. Clinical effects of FMOX against 12 cases of bacterial infections were excellent in 6 cases, good in 5 cases and poor in 1 case, thus the clinical efficacy rate was 91.7%. FMOX was also given to 6 cases for prophylaxis and prophylactic effects were observed in all the cases. 4. No adverse effects were observed in the 21 cases examined, but elevations of S-GOT and S-GPT were found in 1 case. The abnormal laboratory test results were probably due to this drug.     

Pharmacokinetic and clinical studies on flomoxef in neonates and premature infants]

Studies were made on pharmacokinetics, clinical effects and influence on intestinal bacterial flora in neonates upon administration of flomoxef (FMOX), and the results obtained are summarized as follows: 1. Serum concentrations of FMOX after intravenous administration of 20 mg/kg/dose were 48.5 micrograms/ml in 30 minutes, 33.0 micrograms/ml in 1 hour and 7.3 micrograms/ml in 6 hours. The T 1/2 was 2.7 hours. FMOX at a dose of 40 mg/kg was given to only one new born baby on the 1st day after birth, and serum concentrations were 73.6 micrograms/ml in 30 minutes, 55.9 micrograms/ml in 1 hour and 16.9 micrograms/ml in 6 hours. The T 1/2 was 4.60 hours. 2. FMOX was administered to 21 neonates between 0 and 32 days of age. Clinical effects were evaluable in 8 of 21 cases. The results were excellent in 2 cases, good in 5 cases and poor in 1 case. Of the 21 cases, diarrhea in 1 case, elevation of eosinophile in 2 cases (9.5%), elevation of platelet count in 3 cases (14.3%), and elevation of GOT in 2 cases (9.5%) were recognized during treatment. 3. FMOX was detected in feces at levels of 0.84-44.4 micrograms/g. Except for a slight decrease in numbers of anaerobes, little fluctuations of intestinal flora were observed during treatment.     

Pharmacokinetic studies on ceftazidime in neonates

The pharmacokinetics of ceftazidime (CAZ) were investigated in neonates. The following was a summary of the results obtained. Mean peak serum levels of CAZ reached at 15 minutes after intravenous administrations at single doses of 10 mg/kg were 31.7 micrograms/ml in 1-day-old neonates and 31.4 micrograms/ml in a 13-day-old neonate. Mean serum levels at 6 hours after administrations were 8.97 micrograms/ml and 5.26 micrograms/ml in the 1-day-old and the 13-day-old, respectively. Mean half-lives of CAZ in sera were 3.29 hours in the 1-day-old and 2.24 hours in the 13-day-old. In a 4-day-old neonate, the serum level of CAZ reached a peak of 25.4 micrograms/ml at 1 hour and was 5.75 micrograms/ml at 6 hours; the half-life was 2.41 hours. Peak serum levels of CAZ reached at 15 minutes after intravenous administrations at single doses of 20 mg/kg were 46.3 micrograms/ml in a 3-day-old neonate and 80.6 micrograms/ml in a 7-day-old neonate. The serum levels at 6 hours after administration were 12.2 micrograms/ml and 10.4 micrograms/ml, in the 3-day-old and the 7-day-old, respectively. Half-lives of CAZ in sera were 3.02 hours in the 3-day-old and 2.08 hours in the 7-day-old. In 4-day-old neonates, mean serum levels were 52.5 micrograms/ml at 15 minutes and 14.6 micrograms/ml at 6 hours after administration and the half-life was 2.76 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic, bacteriological and clinical studies on imipenem/cilastatin sodium in neonates

Pharmacokinetic, bacteriological and clinical studies on imipenem/cilastatin sodium (IPM/CS) were performed in neonates. The results obtained are summarized as follows. 1. Plasma levels and urinary excretion of IPM and CS sodium were determined in 7 neonates with ages between 7 and 26 days (gestation periods were 37 to 41 weeks and birth weights were 2,410 to 3,890 g) upon 1 hour drip intravenous infusion of IPM/CS at 10 mg/10 mg/kg, or 20 mg/20 mg/kg. Mean plasma concentrations of IPM reached their peaks at the end of infusion with levels of 12.7 +/- 3.0 micrograms/ml for the group given 10 mg/10 mg/kg, and 19.1 +/- 4.1 micrograms/ml for 20 mg/20 mg/kg. The concentration of IPM in plasma showed a dose-response to the 10 mg/10 mg/kg and 20 mg/20 mg/kg dosages. Concentrations decreased with half-lives of 1.87 +/- 0.71 hours and 1.97 +/- 0.21 hours for the low and the high dosages, and plasma levels at 8 hours after administration were 0.3 +/- 0.1 microgram/ml and 0.8 +/- 0.3 microgram/ml, respectively. Mean urinary recovery rates in 8 hours after administration were 37.6 +/- 11.8% and 26.8 +/- 17.2% for the low and the high dosages. While, mean plasma concentrations and mean urinary recovery rates of CS were higher than those of IPM, mean plasma half-lives of CS were similar to IPM. 2. IPM/CS was administered to 11 neonatal patients (with ages between 1 and 26 days) of various bacterial infections, and clinical effectiveness, bacteriological efficacy and adverse reactions were evaluated. Clinical efficacies in cases including 7 with acute pneumonia and 1 each with suspected septicemia, intrauterine infection, acute urinary tract infection and periproctal abscess were judged excellent in 10 and good in 1 case, and the efficacy rate was 100%. Causative organisms isolated from these patients included 3 strains of Escherichia coli and 1 strain each of Streptococcus pyogenes, Streptococcus agalactiae Enterococcus faecalis and Haemophilus influenzae. All the organisms were eradicated by IPM/CS, thus the bacteriological eradication rate was 100%. No adverse reactions were observed, but decreased platelet in 1 patient and increased GOT in 2 patients were found as abnormal laboratory test values. These changes, however were transient, and returned to normal after discontinuation of IPM/CS. It was concluded that the clinical results of IPM/CS are indicative of excellent efficacy, safety and usefulness of the drug in the treatment of infections in neonates.     

Pharmacokinetic and clinical studies on imipenem/cilastatin sodium in neonates and premature infants

Imipenem/cilastatin sodium (IPM/CS) was administered in a dose of 10 mg/10 mg/kg or 20 mg/20 mg/kg by a 1-hour intravenous drip infusion to 19 mature and premature neonates with ages from 1 to 12 days with various bacterial infections, and plasma concentrations and urinary recovery rates in these subjects were measured. Because of the small number of patients recruited, neonates were not divided into mature and premature groups, but into 3 groups based on their day-ages: 0-3 days, 4-7 days and 8 days or older. A clinical evaluation of IPM/CS was carried out in 10 male and 3 female neonates with ages 0-28 days. These patients included 6 with pneumonia, 4 with urinary tract infection and 1 each with septicemia, suspected septicemia and maxillary sinusitis. 1. Plasma concentrations and urinary recovery rates (1) The 1-hour intravenous drip infusion at 10 mg/10 mg/kg of IPM/CS IPM: Its peak plasma concentrations were obtained at the end of drip infusion of the test drug in all 3 groups, their values ranged from 18.18 to 19.90 micrograms/ml with no statistically significant variations. The plasma concentrations rapidly decreased to 0.32-0.98 microgram/ml at 8 hours after administration of IPM/CS. The half-lives tended to be shorter in older neonates, with mean half-lives being 1.87, 1.55 and 1.40 hours, respectively. CS: Its peak plasma concentrations were obtained for all 3 groups at the end of drip infusion and were ranging from 28.23 to 30.00 micrograms/ml with no significant variations. Plasma concentrations in the 0-3 day-age group and the 4-7 day-age group slowly decreased to 6.30 micrograms/ml and 4.58 micrograms/ml at 8 hours after administration of IPM/CS, respectively. Half-lives were 4.10 hours and 3.08 hours, respectively. On the other hand, those of the 8-day or older group rapidly decreased to below the detection limit in 8 hours after administration with a half-life of 1.6 hours. (2) The 1-hour intravenous drip infusion at 20 mg/20 mg/kg of IPM/CS IPM: Peak plasma concentrations were obtained in all 3 groups at the end of drip infusion and were ranging from 31.1 to 38.24 micrograms/ml. Plasma concentrations rapidly decreased, and were 0.95-2.08 micrograms/ml at 8 hours after administration with half-lives of 1.5-1.88 hours. CS: Peak plasma concentrations were obtained in all 3 groups at the end of drip infusion and were ranging from 47.0 to 55.82 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)