[Analysis of multiple cephalosporins in blood and urine by HPLC].

OBJECTIVE: To establish a new high performance liquid chromatography (HPLC) method for determining the concentration of cefazolin, cefradine, cefoperazone and cefotaxime in blood and urine, as well as to investigate its applicability. METHODS: Protein in blood and urine was precipitated directly by acetonitrile with acetanilide was used as the internal standard using Agilent Zorbax SB-Aq column (250 mm x 4.6 mm, 5 microm). The mixed solvents of water (triethylamine 0.12%, acetic acid 0.12%) and acetonitrile were used as the mobile phase to separate cephalosporins using gradient elution method at 1 mL/min (flow rate) and 254 nm (detection wavelength). RESULTS: The working curve of four cephalosporins showed a good correlation (r = 0.9993), with the detection limit up to 0.01 microg/mL. The recovery rate was more than 81.2%. CONCLUSION: This method is fast, easy and accurate. It is suitable for biological analysis of the 4 cephalosporins of the blood and urine in practical cases.

Subcutaneous pharmacokinetics and dosage regimen of cefotaxime in buffalo calves (Bubalus bubalis).

The pharmacokinetics and dosage regimen of cefotaxime following its single subcutaneous administration (10 mg/kg) were investigated in buffalo calves. Plasma and urine samples were collected over 10 and 24 h post administration, respectively. Cefotaxime in plasma and urine was estimated by microbiological assay technique using E. coli as test organism. The pharmacokinetic profiles fitted one-compartment open model. The peak plasma levels of cefotaxime were 6.48 +/- 0.52 microgram/ml at 30 min and the drug was detected upto 10 h. The absorption half-life and elimination halflife were 0.173 +/- 0.033 h and 1.77 +/- 0.02 h, respectively. The apparent volume of distribution and total body clearance were 1.17 +/- 0.10 l/kg and 0.45 +/- 0.03 l/kg/h, respectively. The urinary excretion of cefotaxime in 24 h, was 5.36 +/- 1.19 percent of total administrated dose. A satisfactory subcutaneous dosage regimen for cefotaxime in buffalo calves would be 13 mg/kg repeated at 12 h intervals.

Single-dose ceftriaxone kinetics in the newborn.

Ceftriaxone kinetics were characterized after a single, 2-minute, intravenous infusion of 50 mg/kg to 20 sick infants 1 to 8 days old who weighed 1.78 to 4.36 kg. Plasma binding parameters could be determined by equilibrium dialysis in 16 of the infants, in whom kinetic parameters for free ceftriaxone in plasma were also determined. Compared with corresponding values in adults, the elimination t1/2 was longer in infants (19 and 8.4 hours) because of reduced total systemic clearance (4.48 and 8.51 ml/min/m2). The apparent steady-state volume of distribution was of the same order in infants and adults (5,130 and 5,350 ml/m2). Both renal and nonrenal clearance of free ceftriaxone were reduced in infants, but these decreases were partially offset by an increased free fraction; plasma binding affinity and capacity constants for infants were about half the adult values. The mean fraction of dose excreted unchanged in urine was estimated at 70% in the neonates and 46% in adults. There were no clinically significant correlations between the kinetic parameters and either age since birth or age since conception. The fraction of free ceftriaxone in plasma inversely correlated with age since conception and was lower in female infants, which decreased the systemic clearance and volume of distribution of total drug in the female infants compared with the male infants. Values for the volume of distribution and clearance parameters were not related to body size (weight or body surface area). From our results, a ceftriaxone dosage of 50 to 100 mg/day is recommended during the first week of life for newborn infants who weigh between 1.8 and 4.4 kg. Impaired renal function may require a reduction in dosage.

Pharmacokinetics of intravenous and intraperitoneal cefotaxime in chronic ambulatory peritoneal dialysis.

We investigated the kinetics of cefotaxime in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 1 gm iv dose was injected and a 1 gm dose was given intraperitoneally in the CAPD fluid during a 4-hour dwell time. Cefotaxime and desacetylcefotaxime were assayed by HPLC. After intravenous injection the cefotaxime serum kinetic parameters were as follows: plasma t 1/2, 2.31 +/- 0.20 hours; volume of distribution, 0.35 +/- 0.04 L/kg; total plasma clearance, 118.7 +/- 12.3 ml/min; and peritoneal clearance, 6.7 +/- 1.3 ml/min. Dialysate cefotaxime concentrations rose rapidly, but only 5% of the dose was eliminated by the peritoneal route. After intraperitoneal instillation, cefotaxime appeared in the serum rapidly and the peak serum concentrations ranged from 9 to 20 micrograms/ml between 1 and 3 hours. The absorption of cefotaxime from peritoneal space was 58.7% +/- 5.4%. Data suggest that cefotaxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of cefotaxime in CAPD fluid may permit rapid absorption to achieve therapeutic serum concentrations.

Cefotaxime and desacetyl cefotaxime kinetics in renal impairment.

Cefotaxime and desacetyl cefotaxime kinetics after a single, 1 gm intravenous dose were evaluated in five groups of subjects: group I, normal creatinine clearance (CLCR greater than 90 ml/min); group II, mild renal insufficiency (CLCR 30 to 89 ml/min); group III, moderate renal insufficiency (CLCR 16 to 29 ml/min); group IV, severe renal insufficiency (CLCR 4 to 15 ml/min); and group V, end-stage renal disease requiring maintenance hemodialysis (CLCR less than 6 ml/min). The steady-state volume of distribution (Vss) ranged from 10% to 55% of body weight but was not related to CLCR. The terminal t1/2 values of cefotaxime and desacetyl cefotaxime were 0.79 and 0.70, 1.09 and 3.95, 1.55 and 5.65, 2.54 and 14.23, and 1.63 and 23.15 hours in groups I to V, respectively. There were no significant changes in Vss or t1/2 after multiple dosing, but there were significant correlations between CLCR and cefotaxime total body clearance, cefotaxime and desacetyl cefotaxime renal clearance, and cefotaxime nonrenal clearance. Dosage regimens for the use of cefotaxime in patients with renal impairment are proposed.

Pharmacokinetic study of cefmenoxime (SCE 1365-CMX) in healthy adults.

Cefmenoxime pharmacokinetics were investigated in six healthy volunteers after intravenous and intramuscular administration of 0.5, 1, and 2 g. Blood and urine samples were analyzed by reversed-phase high-pressure liquid chromatography using ultraviolet detection at 275 nm. The assay is precise and linear up to 200 micrograms/ml-1, with 0.02 micrograms/ml-1 as the limit of detection. Linearity of cefmenoxime kinetics was demonstrated because the area under the plasma concentrations is proportional to studied doses. Eight hours after 1 g of cefmenoxime intramuscularly, mean plasma concentrations are, respectively, 0.6 +/- 0.1 and 0.3 +/- 0.1 microgram/ml-1. Intramuscular cefmenoxime is rapidly absorbed (Ka = 7.28 hours-1) with complete bioavailability (F = 0.99); apparent volume of distribution is 0.35 liters/kg-1 and elimination half-life 1.5 hours. The fraction of cefmenoxime excreted unchanged in the urine after intramuscular administration is 0.72, indicating a major contribution of renal clearance in total clearance. Experimental data after intramuscular administration were well fitted with a two-compartment model.

Dose linearity and other pharmacokinetics of cefodizime after single-dose intravenous administration.

Pharmacokinetics of cefodizime, a broad-spectrum cephalosporin antibiotic, were determined after intravenous (IV) administration of single doses of 1.0, 1.5, and 2.0 gm to 12 healthy male volunteers in an open study. In a separate pilot study, data were obtained after IV administration of 0.5 gm of cefodizime to six healthy male volunteers. Determinations of cefodizime in serum and urine using a microbiological assay agreed with determinations using high-pressure liquid chromatography (HPLC), which specifically measures the unchanged drug. Active metabolites of cefodizime were not detected. After IV administration of 1.0, 1.5, and 2.0 gm of cefodizime, initial mean serum concentrations were 215, 322, and 394 mg/L, respectively (HPLC determinations). A linear response to dosage was shown (coefficient of correlation r = .89), as was the case for area under the serum concentration-time curve to infinity, AUC infinity (r = .82), and 48-hour urinary recovery of cefodizime (r = .94). In all cases, the corresponding values obtained after the 0.5-gm dose showed that the linearity extended to this dose. The kinetics of single-dose administration of cefodizime corresponded to a two-compartment open model with an apparent steady-state volume of distribution of about 40 L. Volume of distribution, terminal elimination half-life, serum and renal clearance, and percent urinary recovery were not dose dependent. Cefodizime combined a long terminal elimination half-life (mean, 2.5 hours) with a high urinary recovery (80%). After IV administration of cefodizime, urinary concentrations of the unchanged drug remained above 5 micrograms/ml for at least 24 hours after drug administration and were dose dependent. Mean values for the 1.0-gm and 2.0-gm doses were, respectively, approximately 12 mg/L and 30 mg/L, several times the minimal inhibitory concentrations (MIC90) for most clinically relevant bacteria. These results suggest that once- or twice-daily IV dosing with cefodizime (depending on the dose regimen) would be suitable for clinical use. The drug was safe and well tolerated.

NONMEM analysis in determining the tri-exponential disposition of cefotaxime: a method of evaluating serum and urinary phase I data.

The time above the minimum inhibitory concentration (MIC) is an important surrogate parameter for the efficacy of cephalosporines. In clinical practice cefotaxime (CTX) is usually administered every 8 h or 12 h. Unfortunately the limit of quantification (LOQ) of the available assay is not low enough to detect CTX concentrations in serum later than 6 h after a 2 g i.v. dose. Consequently the time above MIC has to be estimated by extrapolation of the available serum data. Due to the concentrating properties of the kidney, concentrations in urine following a 2 g dose however remain above the LOQ for up to 16 h. It is therefore possible to follow the pharmacokinetics of CTX in urine within a 12 h dosing interval. Due to the linear pharmacokinetics of CTX, serum concentrations, and accordingly the time above MIC, can be estimated by using the measured urinary excretion and the calculated renal clearance. The pharmacokinetics of cefotaxime were studied in 12 healthy subjects who received a single 2 g i.v. dose administered as a short infusion. Blood and fractional urine were collected up to 24 h after dosing. For the characterization of the true terminal half-life only sparse and unbalanced serum and urinary data was available. In such situations, the population approach is the method of choice for estimating the kinetic parameters. The combined analysis of serum and urinary data using NONMEM shows the superiority of a tri-exponential compared to a bi-exponential pharmacokinetics model. As a result, the predicted serum trough levels of cefotaxime following twice daily dosing are about 30-fold higher than those extrapolated from the bi-exponential model. Consequently, the concentrations of CTX- and its metabolite desacetyl-CTX--are above the MIC of many therapeutically relevant pathogens for a longer period of time than previously assumed. In conclusion, a twice daily dosing regimen for cefotaxime is adequate for a number of clinically relevant pathogens. This is supported by the positive outcome in previous clinical trials following this dosing regimen.

Comparison of the renal excretory mechanisms of cefmenoxime and other cephalosporins: effect of para-aminohippurate on renal clearance and intrarenal distribution of cephalosporins in rabbits.

The renal excretory mechanism of cefmenoxime in rabbits was compared with that of 6 other cephalosporins (cefotaxime, deacetylcefotaxime, cefotiam, cefazolin, cephaloridine, and cefsulodin). The clearance ratios (Cf-Drug/CInulin=CRf) of cefmenoxime (337) and cefazolin (73) were considerably higher than those of the 5 other cephalosporins (0.9-20). When p-amino-hippurate (PAH) was administered concurrently with each of the cephalosporins, the CRf values of the cephalosporins except for cefsulodin were significantly decreased. These findings indicate that cefmenoxime and the 5 other cephalosporins except cefsulodin are actively incorporated in the proximal tubular cells and secreted into the tubular lumen. In the case of cefotiam and cefsulodin, glomerular filtration tended to exceed urinary excretion with highest dose of PAH (40 mg/kg/minute), suggesting the possibility of tubular reabsorption of these drugs. On the other hand, glomerular filtration of cefmenoxime and the 4 other cephalosporins did not exceed urinary excretion. The drug concentration ratio of the cortex to medulla indicated that the tubular cell level of cefmenoxime was lower than, higher than, and similar to those of cephaloridine, cefotaxime, and the remaining cephalosporins, respectively. These results demonstrate that the renal excretory mechanisms of cefmenoxime is similar to that of cefazolin but not to that of the remaining cephalosporins.

Parameters characterizing the in vitro activity of cefixime, a new oral broad spectrum cephalosporin, against respiratory and urinary pathogens.

The wide and potent in vitro activity of cefixime, a new oral broad spectrum cephalosporin, has been confirmed on a collection of respiratory and urinary pathogens recently isolated in Italy. The new cephem emerged as the most bactericidal of all the comparators tested against several fast as well as slowly-growing gram-negative species including Enterobacteria, Haemophilus and Moraxella, irrespective of their ability to synthetize beta-lactamases. Among the gram-positive species Streptococcus pyogenes and S. pneumoniae were effectively covered. Cefixime activity was not adversely influenced by several important variables such as pH (over the range from 5 to 8), inoculum size (from 10(5) to 10(8) CFU per ml) and the presence of 50% human serum or urine. Time-kill tests confirmed a pronounced bactericidal potency of the drug especially towards common respiratory pathogens (H. influenzae, M. catarrhalis, S. pneumoniae and S. pyogenes). Killing of urinary strains was optimal at cefixime concentrations reached in urine since eradication, except for Proteus mirabilis, was enhanced with increasing levels of the drug. The absence of an untoward paradoxic effect on the rate of cefixime bactericidal action was confirmed by employing a dynamic bladder model simulating the pharmacokinetic parameters of the drug after a single 200 mg daily dosage. Interactions of cefixime with several other drugs that may be employed in combination therapy were generally prone to provide indifference and synergism while antagonism was never observed. Favorable interactions were also registered when cefixime acted with other antibiotics on partially resistant species such as Staphylococci and Pseudomonas. The new cephem seems to provide excellent opportunities for expanding oral cephalosporin therapy to a wide range of infections produced by susceptible pathogens in the adult and pediatric populations.

[Kinetic and clinical studies on a new cephalosporin: Cefotiam]. / Ricerca cinetica e clinica su una nuova cefalosporina: Cefotiam.

Kinetic and clinical evaluation of cefotiam, a new cephalosporin, is reported. It was found that the drug is rapidly distributed to the tissues. Equilibrium between tissues and plasma is reached in about an hour. Some 90-91% of the dose administered is excreted in the urine, and accumulation does not occur. A clinical cure was obtained in 27 of a series of 35 patients (77.1%). Improvement was observed in 7 cases (20%). The antibiotic proved ineffective in the remaining cases (2.8%). Tolerance was excellent and there were no side-effects worthy of note.

Treatment of complicated urinary tract infections with the long acting cephalosporin, ceftriaxone.

Ceftriaxone, a new broad spectrum cephalosporin with a long biological half-life has been used on a single intravenous daily dosage regimen over a five day period to treat complicated urinary tract infection. Bacteriological analysis of urine up to six weeks after such treatment, indicated that ceftriaxone was successful in 13 out of 15 cases treated compared with two out of 15 cases treated with cefuroxime given three times daily over the five day treatment period.

[A clinical study on postantibiotic effect (PAE) and its application to chemotherapy for complicated cystitis with an automatic simulator of urinary drug concentration].

In an in vitro complicated cystitis model, the concentrations of the urinary antimicrobial agents were determined using a computer-controlled automatic urine concentration simulator. The effects on the bacterial count curves showing the presence or absence of PAE in antimicrobial agents were studied by comparing the times required for regrowth to the concentration at the initial inoculation, i.e., effective regrowth time (ERT). The following results were obtained. 1. When beta-lactam antimicrobial agents (such as AMPC and CFIX) with no PAE against the gram-negative rods were tested, the ERT of the gram-negative rods were about two hours shorter than that of the gram-positive coccus. 2. When new quinolone antimicrobial agents (such as OFLX) and aminoglycosides (such as ISP) that possess PAE against both the gram-positive and negative organisms were used there was no difference between ERT of the gram-negative rods and gram-positive coccus. Therefore, it was demonstrated that the presence or absence of PAE is also reflected in the cell number curve in the case of this in vitro model, more closely related to clinical cases, when the antibiotics is simulated in urinary concentration shifting.

[Assay of cefotaxime and desacetylcefotaxime in plasma and urine by high performance liquid chromatography]. / Dosage du céfotaxime et du désacétylcéfotaxime dans le plasma et l'urine par chromatographie liquide haute performance.

The authors propose an assay technique for cefotaxime and desacetylcefotaxime in the plasma and urine, using high performance liquid chromatography. The proteins are precipitated by adding propanol-2 to 100 microliter of plasma or urine. After centrifugation, the supernatant is extracted by a mixture of chloroform and isoamyl alcohol. The cephalosporins remain in the superior aqueous phase and a fraction of this phase is injected into the chromatograph. The cefotaxime, desacetylcefotaxime and cephaloridine (internal standard) are separated on a Radial Pak C 18 column by ion-binding chromatography. The mobile phase consists of a mixture of distilled water and acetonitrile (830/170, V/V) with the addition of an ampoule of Pic A (tetrabutylammonium phosphate). This rapid, specific and sensitive micro-method can be used for the assay of these antibiotics in adults and children, for therapeutic monitoring and for pharmacokinetic studies.

[Determination of cefixime in human plasma and urine using high performance liquid chromatography column switching technique].

A double column and double pump HPLC switching system is described for the analysis of cefixime in human plasma and urine. The system used muBondapak C18 short pretreatment column for on-line sample clean-up and a Hitachi GEL 3056 (ODS) analytical column for separation. A mixed solution of 0.01 mol/L H3PO4-0.1 mol/L KH2PO4-H2O (20:1:79) was used as the pretreatment mobile phase and CH2CH-0.01 mol/L H3PO4-0.1 mol/L KH2PO4-H2O (13:20:1:66) was used as analytical mobile phase. The compound in plasma and urine is detected by ultraviolet absorption at 286 nm and 314 nm, respectively. The absolute recoveries of the method in plasma and urine were 99.1% and 98.6% respectively. The relative standard deviations of the method are 0.70-3.82% and 0.80-3.73% in plasma, 1.53-3.08% and 1.31-2.67% in urine between days and day-to-day. Linear calibration curve for cefixime was measured over the range of 0.1-3.2 micrograms/ml in plasma and 1.0-32.0 micrograms/ml in urine, and the correlation coefficients were all 0.9999. The detection limit was 0.05 micrograms/ml in plasma and 0.2 micrograms/ml in urine. The plasma and urine samples were diluted with water and injected directly onto the HPLC system. The operation is simple and the relative sensitivity is markedly increased because of higher recoveries and larger loading capacity of the sample.

[Studies on the pharmacokinetics of cefotaxime in neonates].

The pharmacokinetics of cefotaxime was investigated in neonates. The following results were obtained. 1. The peak serum concentration of cefotaxime, seen 15-minutes after a single intravenous of 20 mg/kg, was 51.6 +/- 9.3 mcg/ml by bioassay. After 6 hours the mean serum concentration decreased to 5.6 +/- 3.1 mcg/ml. Concentrations obtained by HPLC paralleled those determined by bioassay. The peak serum concentration of the desacetyl metabolite was attained 30 minutes to 2 hours after injection. The mean serum desacetyl metabolite concentration was about 1/2.5 times higher than the cefotaxime concentration. The half-life was inversely related to the age of the neonates, decreasing to 1.64 hours on day 11 postpartum. 2. Serum concentrations determined by bioassay and HPLC after administering a dose of 10 mg/kg of cefotaxime by 30-minute intravenous drip infusion were comparable. The peak serum concentration at the completion of intravenous drip infusion was 21.0 mcg/ml by bioassay. The half-life of cefotaxime was 2.85 hours. The peak serum concentration of the desacetyl metabolite, seen at the completion of intravenous drip infusion, was about 1/2 times that of the peak cefotaxime concentration. 3. The peak serum concentration at the completion of a 30-minute intravenous drip infusion of 20 mg/kg displayed a mean value of 33.5 +/- 10.3 mcg/ml by bioassay. After 6 hours the mean serum concentration was 4.0 +/- 1.0 mcg/ml. The peak serum concentration of the desacetyl metabolite, seen at the completion of infusion to 2 hours thereafter, was equivalent to about 1/2.2 the peak cefotaxime concentration. 4. Mean urinary excretion rate of cefotaxime in 2-day-old neonates was 23.4% by bioassay 6 hours after a 30-minute intravenous drip infusion of 10 mg/kg. The mean urinary excretion rate of the desacetyl metabolite was 8.7%. Mean 6-hour excretion rates in 2-day-old and 4-day-old neonates administered 20 mg/kg of cefotaxime by 30-minute intravenous drip infusion were 6.2% and mean 37.7%, respectively. The corresponding values for the desacetyl metabolite were 2.4% and 12.4%, respectively.

[Basic studies of cefmenoxime].

Blood levels and urinary excretion of cefmenoxime (CMX) in children of 8 to 13 years old who received 50 mg/kg of CMX by one shot intravenous injection or 1-hour drip infusion were evaluated. One shot intravenous injection (1) Blood levels--The mean blood levels in 2 cases by intravenous injection were 125.0 +/- 24.0, 56.8 +/- 10.0, 17.8 +/- 6.2, 2.2 +/- 0.7 and 0.4 +/- 0.2 micrograms/ml, after 1/2, 1, 2, 4 and 6 hours, respectively. The mean biological half-life was approximately 0.7 hour. (2) Urinary excretion--The average urinary excretion rate in 2 cases were 57.8, 63.9 and 64.1% after 2, 4 and 6 hours, respectively. 1-hour drip infusion (1) Blood levels--The mean blood levels in 2 cases by drip infusion were 115.5 +/- 0.5, 29.05 +/- 0.25, 5.0 +/- 0.8 and 1.15 +/- 0.45 micrograms/ml, immediately after the completion of infusion, after 1, 3 and 5 hours, respectively. The mean biological half-life after drip infusion was approximately 0.8 hour. (2) Urinary excretion--The average urinary excretion rate in 2 cases were 42.2, 55.5 and 56.5% after 2, 4 and 6 hours, respectively. On the basis of these results, it was concluded that CMX was excreted relatively rapidly in a massive dose of 50 mg/kg a time.

[Pharmacokinetic studies on oral antibiotics in pediatrics. I. A pharmacokinetic study on cefixime in pediatrics].

A pharmacokinetic study on cefixime (CFIX) 5% granules for pediatric use was performed, and pharmacokinetic parameter were calculated. 1. Six school children were administered orally with CFIX granules at a dose level of 3 mg/kg either at 30 minutes before meal or at 30 minutes after meal on a crossover design, and serum concentrations and urinary excretion rates of CFIX were determined. Tmax, Cmax, T 1/2 and urinary excretion rate (0-12 hours) following the administration before meal were 3.33 +/- 0.42 hours, 1.03 +/- 0.17 micrograms/ml, 2.31 +/- 0.26 hours and 15.3 +/- 2.2%, respectively, Tmax, Cmax, T 1/2 and urinary excretion rate following the the administration after meal were 4.00 +/- 0.52 hours, 0.90 +/- 0.09 micrograms/ml, 3.11 +/- 0.21 hours and 11.3 +/- 1.6%, respectively. Earlier Tmax, higher Cmax and higher urinary excretion rate were observed when the drug was administered before meal than when administered after meal. These differences between the 2 groups were not statistically significant. 2. Five school children were administered orally with CFIX granules at 30 minutes after meal at a dose level of either 3 mg/kg or 6 mg/kg on a crossover design, and serum concentrations and urinary excretion rates of CFIX were determined. Cmax and AUC at a dose level of 3 mg/kg were 1.01 +/- 0.26 mg/ml and 5.86 +/- 1.13 micrograms.hr/ml, respectively, and Cmax and AUC at a dose level of 6 mg/kg were 1.76 +/- 0.29 micrograms/ml, 12.54 +/- 1.77 micrograms.hr/ml, respectively. A dose response relationship was thus observed. Seven infants (3 mg/kg) and 3 infants (6 mg/kg) were administered orally with CFIX granules at 30 minutes after meal. Cmax and AUC at a dose level of 3 mg/kg were 2.45 +/- 0.26 micrograms/ml, 33.50 +/- 7.62 micrograms.hr/ml, respectively, and Cmax and AUC at a dose level of 6 mg/kg were 4.42 +/- 0.98 micrograms/ml, 66.85 +/- 25.19 micrograms.hr/ml, respectively. A dose response was observed. 3. Eleven school children, 5 younger children and 7 infants were administered orally with CFIX granules at a dose level of 3 mg/kg at 30 minutes after meal, and serum concentrations and urinary excretion rates of CFIX were determined. Tmax in school children, younger children and infants were 3.82 +/- 0.33 hours, 5.20 +/- 0.49 hours and 5.43 +/- 0.37 hours, respectively. Earlier Tmax's were observed in school children than in other children. Cmax in school children, younger children and infants were 0.95 +/- 0.12 micrograms/ml, 0.56 +/- 0.06 micrograms/ml and 2.45 +/- 0.26 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

[Basic studies of cefotiam (author's transl)].

The basic studies of cefotiam (CTM) were performed, and the following results were obtained. 1. One shot intravenous injection of 40 mg/kg of CTM (1) Serum levels: The mean levels of CTM in 3 children were 133.9 micrograms/ml after 15 minutes, 71.5 micrograms/ml after 30 minutes 32.6 micrograms/ml after 1 hour, 9.2 micrograms/ml after 2 hours, 2.5 micrograms/ml after 4 hours, 0.9 microgram/ml after 6 hours. The serum half life of CTM was approximately 1.2 hours on beta-phase. (2) Urinary excretion: The mean urinary excretions were 39.4% over 3 hours, 44.7% over 4 hours, 45.7% over 6 hours. 2. 1 hour-drip infusion of 40 mg/kg of CTM (1) Serum levels: The mean serum levels of CTM in 4 children were 140.1 micrograms/ml at immediately after drip infusion was completed, 10.6 micrograms/ml after 1 hour, 3.8 micrograms/ml after 2 hours, 1.4 micrograms/ml after 3 hours, 0.5 microgram/ml after 5 hours. The serum half life of CTM was approximately 1.0 hour on beta-phase. (2) Urinary excretions: The mean urinary excretions were 42.9% over 2 hours, 48.0% over 4 hours, 48.7% over 6 hours. 3. Bioactive metabolite in serum and urine: No bioactive metabolites were observed in either serum or urine after administration of 40 mg/kg of CTM.

[Clinical studies on ceftizoxime in pediatric field (author's transl)].

Clinical studies on ceftizoxime, a new cephalosporin, were carried out in our department. The following results were obtained. 1. Antibacterial activity. Antibacterial activity of ceftizoxime against 7 strains of E. coli, 6 strains of Klebsiella, 6 strains of H. influenzae, 7 strains of E. cloacae and 10 strains of S. aureus, recently isolated from patients, was compared with that of cefotiam, cefmetazole and cefazolin. Ceftizoxime was more active than the other antibiotics against E. coli, Klebsiella, H. influenzae and E. cloacae, but less active against S. aureus. 2. Urinary excretion. Urinary excretion was measured in 2 cases with normal renal function after dosing with 750 mg (35 mg/kg) and 350 mg (17 mg/kg) of ceftizoxime by intravenous injections. Urinary recovery rates within 6 hours were 97% and 82% respectively. 3. Clinical study. Eighteen children with the following bacterial infections were treated with ceftizoxime; respiratory tract infection (13), acute otitis media (1), acute intervertebral chondritis and tonsillitis (1), chronic cystitis (1), subcutaneous abscess (1) and chronic bacteremia (1). The dosage was 69--147 mg/kg q.i.d. by intravenous injection. The duration of administration was from 3 to 32 days. The clinical results were excellent in 4 cases, good in 13 cases and fair in 1 case of chronic bacteremia. The overall effectiveness rate was 94%. Slight elevation of GPT in 1 case and leukopenia (neutropenia) in 1 case were observed, but returned to the normal range immediately after discontinuation of dosing. It is considered that ceftizoxime is one of the useful first choice antibiotics used for children with bacterial infections.