Doxapram in the treatment of idiopathic apnea of prematurity: desirable dosage and serum concentrations.
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Biomedical subjects
Publications and source records attributed to F Hayakawa.
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Fundamental and clinical studies on imipenem/cilastatin sodium (MK-0787/MK-0791) were performed in pediatric patients with infections. Results obtained were summarized below. The mean plasma half-life of MK-0787 was 0.84 hour with a dosage of 10 mg/kg and 0.90 hour with a dosage of 20 mg/kg. Mean plasma half-lives of MK-0791 were 0.40 hour and 0.71 hour for dosages of 10 mg/kg and 20 mg/kg, respectively. Urinary recovery of both MK-0787 and MK-0791 was high. The antibacterial activity of MK-0787 against clinically isolated organisms was determined. The MK-0787 was bactericidal against a broad spectrum of both Gram-positive and Gram-negative pathogens. The MK-0787/MK-0791 was administered to 32 pediatric patients with various infections. The overall clinical efficacy rate was 96.9%. Side effects observed were loose stools in one patient, diarrhea in another and slight elevations of platelet and direct bilirubin, and eosinophilia were observed in 3 patients, respectively.
Aqueous solutions of thiamin hydrochloride were incubated with catechol for 24 hr, pH 7.4 at 50 degrees C. Additional solutions of thiamin and catechol were incubated separately. After incubation the remaining thiamin was analyzed by the thiochrome procedure which showed that the thiamin in the thiamin-catechol mixture was reduced by 82.5-90% and the thiamin incubated alone by 18-20%. The solutions were fed to groups of rats after they had been on a thiamin free diet for 17 days. Body weight gains, erythrocyte transketolase (ETKA), thiamin pyrophosphate effect (TPPE) and liver and urine thiamin were measured. The results of these experiments showed that given the thiamin-catechol mixture (after incubation at pH 7.4, 50 degrees C for 24 hr) produced thiamin deficiency according to ETKA and TPPE values indicating that the thiamin was unavailable in vivo as well as in vitro. However, rats given thiamin and catechol separately (even after incubated each) no thiamin deficiency was observed.
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Fundamental and clinical studies on cefixime (CFIX), a new oral cephem antibiotic, were carried out in the pediatric field. The results were as follows: Serum concentrations and urinary recovery rates were determined after oral administration of CFIX at doses of 3 mg/kg and 6 mg/kg in 2 cases each (4 cases in total). The mean serum concentrations of CFIX were 0.52 and 0.58 micrograms/ml at 2 hours, 0.80 and 1.42 micrograms/ml at 4 hours, 0.73 and 1.36 micrograms/ml at 6 hours, 0.54 and 1.12 micrograms/ml at 8 hours, respectively. The mean peak serum concentration of CFIX was obtained at 4 hours after administration, with serum half-lives (T1/2) of 3.77 and 5.30 hours, respectively. The mean cumulative urinary recovery rates within 12 hours after administration of CFIX at doses of 3 mg/kg and 6 mg/kg were 8.4% and 6.8%, respectively. Antibacterial activities of CFIX against clinically isolated strains of S. pyogenes, S. pneumoniae. E. faecalis, S. aureus, E. coli, H. influenzae, H. parainfluenzae were compared with those of amoxicillin (AMPC), cefaclor (CCL), and cephalexin (CEX). It was observed that CFIX was a little less active than AMPC against S. pyogenes and S. pneumoniae, but CFIX was more active than CCL and CEX. CFIX was the most active against E. coli, H. influenzae and H. parainfluenzae. Twenty-one pediatric patients with bacterial infections (10, tonsillitis; 4, pharyngitis; and 7, urinary tract infections) were treated with CFIX at doses of 1.5-6.0 mg/kg in 2 or 3 times daily for 4-10 days. The efficacy rate was 95.2% clinically and 91.3% bacteriologically. No adverse reactions were observed. An abnormal laboratory finding (slight elevation of S-GOT and S-GPT) was observed in 1 case.
Laboratory and clinical studies were carried out with aspoxicillin (TA-058, ASPC), a new semisynthetic penicillin, in pediatric infectious disease, and following results were obtained. The average serum concentrations of ASPC after intravenous injection were 53.6, 151.2 micrograms/ml at 15 minutes, 28.0, 72.8 micrograms/ml at 30 minutes, 17.6, 43.3 micrograms/ml at 1 hour, 7.0, 19.9 micrograms/ml at 2 hours, 0.3, 1.8 micrograms/ml at 6 hours, when the doses were 20 mg/kg and 40 mg/kg, respectively. The mean half-lives of ASPC in blood after injection were 0.87 hour and 1.1 hours when the doses were 20 mg/kg and 40 mg/kg, respectively. The mean recovery rates in the urine during 6 hours after intravenous injection of 20 mg/kg and 40 mg/kg were 62.0 and 62.8%, respectively. The antibacterial activity of ASPC against clinically isolated organisms was determined. ASPC had good activity against H. influenzae, H. parainfluenzae, S. pneumoniae and S. pyogenes. Thirty-four patients; 26 cases of respiratory tract infections, 6 cases of urinary tract infections, 1 case of bacterial meningitis and 1 case of bacterial lymphadenitis, were treated with 57.0-159 mg/kg daily dose of ASPC for 4-19 days. The rate of satisfactory clinical response was 85.3%. As to side effects, loose stool was observed in 3 cases, slight elevation of GOT & GPT and elevation of platelet were noted, in 2 cases, respectively. All were transient and considered to be minor.
Clinical evaluation of ceftizoxime suppository (CZX-S), a new antibiotic rectal suppository, was performed in 5 cases with bacterial infections in pediatric field (2 with acute bronchitis, 1 with acute tonsillitis, UTI and pertussis, respectively) and the following results were obtained; Blood levels of CZX at 10-20 minutes after administration of CZX-S at a dose of 10.0-26.3 mg/kg in 5 cases were 3.26-23.3 micrograms/ml and the urinary excretion rates within 6 hours were 15.2, 60.1, 60.2% in 3 of 5 cases measured respectively. Clinical effects were excellent in 3 and good in 2 cases. Slight elevation of GOT and GPT was observed in 1 case. No other side effects were observed. The patients' tolerability against rectal suppository was good. From the above results, we concluded that CZX-S is useful for treating the pediatric patients with various infections.
Fundamental and clinical studies on BRL 25000 granules, containing 2 parts amoxicillin (AMPC) and 1 part clavulanic acid (CVA) (a beta-lactamase inhibitor) were carried out in the pediatric field. Serum concentrations and urinary excretion rates were determined after oral administration of BRL 25000 granules at a dose of 20 mg/kg to 2 children. The mean peak serum concentrations of AMPC and CVA were 4.89 and 2.85 micrograms/ml at 1 hour after administration, with serum half-lives (T 1/2) of 1.15 and 0.89 hours respectively. Mean cumulative urinary excretion rates of AMPC and CVA in the 6 hours after administration were 24.91% and 10.19%, respectively. BRL 25000 granules were also administered at daily doses of 25.1-60.4 mg/kg in 3 divided doses, to 20 pediatric patients with bacterial infections (4 acute tonsillitis, 2 acute pharyngitis, 3 suspected scarlet fever, 3 acute bronchitis, 8 urinary tract infection). The efficacy rate was 100% clinically and 70% bacteriologically. No adverse reactions were observed, however, abnormal laboratory findings were observed in 4 cases (slight elevation of GOT in 2, GPT in 1, eosinophilia in 1).
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Fundamental and clinical studies were carried out with aztreonam (AZT), a new monocyclic beta-lactam antibiotic, in pediatric infections. Results were as follows. The mean half-lives in the vein blood were 1.09 hours, 1.18 hours, 1.22 hours after injection, when the doses were 10, 20 and 40 mg/kg, respectively. Dose response was observed. The average recovery rates in the urine between 0 and 6 hours were 40.2%, 42.3%, 50.8% when the doses were 10, 20 and 40 mg/kg, respectively. The antibacterial activity of AZT against 16 clinical isolates were determined in comparison with those of ABPC, CPZ, LMOX and CTX. Against 8 clinical isolates of E. coli and 3 of H. influenzae, the activity of AZT was equal or superior to that of CPZ, LMOX and CTX, and way by far superior to that of ABPC. Twenty-three pediatric patients received AZT in doses ranging from 48 to 79 mg/kg divided 3 times a day; 12 cases of urinary tract infection, 9 cases of respiratory tract infection and 2 cases of bacterial enterocolitis. The rate of clinical effectiveness was 100%. No side effect was observed. Slight elevation of GOT and GPT were observed in 2 cases, increase of platelet count in 2. All were considered to be transient and mild.
To clarify the mechanism of thiamin degradation by catechol derivatives, thiamin and its analogues were incubated with caffeic acid or catechol in 1/15 M phosphate buffer pH 7.4 at 48 degrees C or 50 degrees C. Using thin-layer chromatography and high-performance liquid chromatography, several unknown intermediates of the reaction product, which may have both pyrimidine and catechol moieties, were detected.
Equimolecular amounts of thiamin and catechol incubated under suitable conditions produced an unknown reaction product isolated as a light yellow powder from the reaction mixture by reverse-phase ODS column chromatography. Elemental analysis of the purified powder showed the molecular formula to be C18H22N4O4S X HCl X H2O in agreement with a molecular ion peak found at m/e 390 in the mass spectrum. These results together with the data of IR and NMR spectrometry possibly show that this material consists of an isomeric mixture of S-3,4- and S-2,3-dihydroxyphenylthiamin (I and II) which probably arise as a result of oxidative addition of the thiol group of thiamin to catechol.
Clinical trials were carried out with sulbactam/cefoperazone (SBT/CPZ) (combination ratio of 1:1) in pediatric infections. Results were as follows. The mean half-lives of SBT and CPZ in the serum following intravenous injection of SBT/CPZ were about 0.7 and 1.2 hours, respectively. Urinary excretions of SBT and CPZ within 6 hours after intravenous injection of SBT/CPZ were 81.9% and 28.1%, respectively. SBT/CPZ was administered to 33 pediatric patients with various infection; 18 respiratory tract infections, 12 urinary tract infections and 3 Salmonella enterocolitis. The overall efficacy rate was 87.9%. In particular, 7 of 8 urinary tract infections caused by beta-lactamase producing organisms were improved after administration of SBT/CPZ. Diarrhea in 8 and soft stool in 3 of 33 patients occurred, and slight elevation of GOT/GPT was observed in 2 patients.
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