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Frontiers in Molecular Biosciences 2022Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications. Structurally, there are two types of five-membered... (Review)
Review
Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications. Structurally, there are two types of five-membered triazoles: 1,2,3-triazole and 1,2,4-triazole. Due to the structural characteristics, both 1,2,3- and 1,2,4-triazoles are able to accommodate a broad range of substituents (electrophiles and nucleophiles) around the core structures and pave the way for the construction of diverse novel bioactive molecules. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities. These are also important in organocatalysis, agrochemicals, and materials science. Thus, they have a broad range of therapeutic applications with ever-widening future scope across scientific disciplines. However, adverse events such as hepatotoxicity and hormonal problems lead to a careful revision of the azole family to obtain higher efficacy with minimum side effects. This review focuses on the structural features, synthesis, and notable therapeutic applications of triazoles and related compounds.
PubMed: 35547394
DOI: 10.3389/fmolb.2022.864286 -
Antimicrobial Agents and Chemotherapy Dec 1983Cefatrizine was administered intravenously and orally at dose levels of 250, 500, and 1,000 mg to normal male volunteers in a crossover study. Intravenous...
Cefatrizine was administered intravenously and orally at dose levels of 250, 500, and 1,000 mg to normal male volunteers in a crossover study. Intravenous pharmacokinetics were dose linear over this range; mean peak plasma concentrations at the end of 30-min infusions were, respectively, 18, 37, and 75 micrograms/ml, total body clearance was 218 ml/min per 1.73 m2, renal clearance was 176 ml/min per 1.73 m2, and mean retention time in the body was 1.11 h. Cumulative urinary excretion of intact cefatrizine was 80% of the dose, and half-lives ranged from 1 to 1.4 h. Steady-state volume of distribution was 0.22 liters/kg. On oral administration, the absolute bioavailabilities of cefatrizine were 75% at 250 and 500 mg and 50% at 1,000 mg. The mean peak plasma concentrations and peak times were, respectively, 4.9, 8.6, and 10.2 micrograms/ml at 1.4, 1.6, and 2.0 h, mean residence times were 2.4, 2.6, and 3.1 h, and mean absorption times were 1.3, 1.6, and 1.9 h. Oral renal clearance and half-life values corresponded well to the intravenous values. Cumulative urinary excretion of intact cefatrizine (as percentage of dose) was 60 at 250 mg, 56 at 500 mg, and 42 at 1,000 mg. It is hypothesized that the lack of oral dose linearity between the 500- and 1,000-mg doses is due to a component of cefatrizine absorption by a saturable transport process. Relative absorption at the high dose would be sufficiently slow that an absorption "window" would be passed before maximum bioavailability could be attained. It is not expected that the observed bioavailability decrease at doses exceeding 500 mg will have any therapeutic significance, since clinical studies are establishing efficacy for a recommended unit dosage regimen of 500 mg.
Topics: Administration, Oral; Adult; Biological Availability; Blood Proteins; Cefatrizine; Cephalosporins; Humans; Infusions, Parenteral; Kinetics; Male; Middle Aged; Protein Binding
PubMed: 6660858
DOI: 10.1128/AAC.24.6.915 -
Antimicrobial Agents and Chemotherapy Aug 1976The susceptibility of 269 isolates of Haemophilus influenzae type b to cefatrizine (BL-S640), ampicillin, and chloramphenicol was evaluated by disk diffusion...
The susceptibility of 269 isolates of Haemophilus influenzae type b to cefatrizine (BL-S640), ampicillin, and chloramphenicol was evaluated by disk diffusion susceptibility tests, using a modified Bauer-Kirby method. Broth dilution susceptibility tests were performed on 88 of these isolates, including all isolates resistant by disk to cefatrizine or ampicillin. Six of the isolates were resistant by disk to cefatrizine (zone size, <16 mm), four were resistant to ampicillin (zone size, <19 mm), and none were resistant to chloramphenicol (zone size, <17 mm). Only two of the six isolates of H. influenzae that were resistant to cefatrizine by disk were resistant to more than 4 mug of drug per ml. The four organisms resistant to ampicillin on disk were resistant, when tested by the broth method, to >128 mug/ml. These four ampicillin-resistant H. influenzae were susceptible to <4 mug of cefatrizine per ml. The two isolates resistant to >4 mug of cefatrizine per ml were susceptible to 0.5 and 2 mug of ampicillin, respectively, per ml. The activity of cefatrizine appears to be comparable in vitro to ampicillin against H. influenzae.
Topics: Ampicillin; Cephalosporins; Chloramphenicol; Culture Media; Haemophilus influenzae; Microbial Sensitivity Tests; Penicillin Resistance; Triazoles
PubMed: 1086634
DOI: 10.1128/AAC.10.2.322 -
Antimicrobial Agents and Chemotherapy May 1976Cefatrizine (SK&F 60771), a new broad-spectrum cephalosporin, was administered in a 0.5-g dose either orally or intramuscularly to volunteers in a crossover study. After... (Comparative Study)
Comparative Study
Cefatrizine (SK&F 60771), a new oral cephalosporin: serum levels and urinary recovery in humans after oral or intramuscular administration--comparative study with cephalexin and cefazolin.
Cefatrizine (SK&F 60771), a new broad-spectrum cephalosporin, was administered in a 0.5-g dose either orally or intramuscularly to volunteers in a crossover study. After oral administration, the average peak serum levels were 5.6 and 22.1 mug/ml for cefatrizine and cephalexin, respectively. The serum half-life of cefatrizine appeared to be more extended than that of cephalexin. Urinary recovery of cefatrizine (35%) was approximately half that of cephalexin (68%) after oral administration. After intramuscular injection of 0.5 g, the average peak serum level of cefatrizine (12.0 mug/ml) was approximately one-fourth that of cefazolin (44.0 mug/ml). The serum half-life after intramuscular injection was 86 min for cefatrizine and 118 min for cefazolin. Urinary recovery was 45% of the intramuscularly administered dose, as compared with cefazolin, which was 74%.
Topics: Administration, Oral; Cefazolin; Cephalexin; Cephalosporins; Humans; Injections, Intramuscular; Male; Time Factors; Triazoles
PubMed: 949177
DOI: 10.1128/AAC.9.5.800 -
Antimicrobial Agents and Chemotherapy Nov 1977Cefaclor (Lilly 99638) and cefatrizine (BL-S640, SK&F 70771) are orally absorbed, broad-spectrum semisynthetic cephalosporins. They were compared in vitro with... (Comparative Study)
Comparative Study
Cefaclor (Lilly 99638) and cefatrizine (BL-S640, SK&F 70771) are orally absorbed, broad-spectrum semisynthetic cephalosporins. They were compared in vitro with cephalexin, cephaloglycin, and cepharadine against a variety of aerobic pathogenic bacteria by an agar dilution procedure. Cefaclor and cefatrizine were found to be similar or superior to cephalexin, cephaloglycin, and cephradine in terms of activity against gram-positive cocci other than enterococci. Only cefatrizine demonstrated any potentially useful activity against some susceptible isolates of enterococci. Cefaclor and cefatrizine also were highly active, equally or more so than the other oral cephalosporins, against several gram-negative species including Escherichia coli, Enterobacter aerogenes, and Klebsiella pneumoniae. None of the cephalosporins were particularly active against Enterobacter cloacae. Both cefaclor and cefatrizine were active against Proteus mirabilis; cefatrizine was uniquely active against indolepositive Proteus species.
Topics: Aerobiosis; Bacteria; Cefatrizine; Cephalexin; Cephaloglycin; Cephalosporins; Cephradine; Drug Resistance, Microbial; In Vitro Techniques; Microbial Sensitivity Tests
PubMed: 921258
DOI: 10.1128/AAC.12.5.609 -
Antimicrobial Agents and Chemotherapy Feb 1979Cefatrizine, a new orally administered cephalosporin, was tested against 400 clinical isolates. Cefatrizine had excellent activity against gram-positive cocci,... (Comparative Study)
Comparative Study
Cefatrizine, a new orally administered cephalosporin, was tested against 400 clinical isolates. Cefatrizine had excellent activity against gram-positive cocci, inhibiting all except enterococci at minimal inhibitory concentrations below 1 mug/ml. Cefatrizine inhibited the majority of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Salmonella at concentrations below 12.5 mug/ml. Although cefatrizine was not hydrolyzed by many beta-lactamases, it did not inhibit a number of strains of Enterobacter, Serratia, or indole-positive Proteus. Cefatrizine was more active than cephalothin or cephalexin against E. coli, Klebsiella, Enterobacter, Citrobacter, Salmonella, and Shigella. Its overall activity was less than that of cefoxitin against strains resistant to cephalothin, but its activity against cephalothin-susceptible strains was equivalent to that of cefamandole.
Topics: Bacteria; Cefatrizine; Cephalosporinase; Cephalosporins
PubMed: 426514
DOI: 10.1128/AAC.15.2.209 -
Antimicrobial Agents and Chemotherapy Aug 1977To evaluate maternal-fetal pharmacology of cefatrizine (BL-S 640), a new oral cephalosporin, a single oral 1,000-mg dose was administered to 33 gravidas (8 to 20 weeks'...
To evaluate maternal-fetal pharmacology of cefatrizine (BL-S 640), a new oral cephalosporin, a single oral 1,000-mg dose was administered to 33 gravidas (8 to 20 weeks' gestation) at varying intervals within 46 h of an elective therapeutic abortion by hysterectomy or intra-amniotic prostaglandin F(2a) induction. Mean maternal serum concentrations at 1, 2, 4, and 8 h were 3.7, 7.9, 6.5, and 1.6 mug/ml; beyond a 3-h peak, a half-life of 2.4 h was determined. Cefatrizine placental half-life was 4.4 h. None of the 11 fetuses from a prostaglandin F(2a) abortion revealed cefatrizine activity; in contrast, 17 of 22 fetuses from a surgical abortion demonstrated cefatrizine concentrations in two or more samples. Fetal cefatrizine levels were less than 3 mug/g or mug/ml in kidney and urine, less than 2 mug/ml in serum and bile, and less than 2.5 mug/g in lung. After a single maternal dose, cefatrizine has a wide distribution in the fetus in the first half of gestation.
Topics: Amniotic Fluid; Anti-Bacterial Agents; Bile; Brain; Cephalosporins; Female; Fetus; Humans; Kidney; Liver; Lung; Maternal-Fetal Exchange; Placenta; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second
PubMed: 900920
DOI: 10.1128/AAC.12.2.231 -
Pharmaceuticals (Basel, Switzerland) May 2021This case-non-case study aims to detect signals not currently listed on cephalosporin drug labels. From 2009 to 2018, adverse event (AE) reports concerning antibacterial...
This case-non-case study aims to detect signals not currently listed on cephalosporin drug labels. From 2009 to 2018, adverse event (AE) reports concerning antibacterial drugs (anatomical therapeutic chemical (ATC) code J01) in the Korea Adverse Events Reporting System (KAERS) database were examined. For signal detection, three indices of disproportionality, proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC), were calculated. The list of signals was compared with ADRs on the drug labels from the United States, United Kingdom, Japan, and South Korea. A total of 163,800 cephalosporin-AE combinations and 72,265 all other J01-AE combinations were analyzed. This study detected 472 signals and 114 new signals that are not included on the drug labels. Cefatrizine-corneal edema (PRR, 440.64; ROR, 481.67; IC, 3.84) and cefatrizine-corneal ulceration (PRR, 346.22; ROR, 399.70; IC, 4.40) had the highest PRR, ROR, and IC among all signals. Additionally, six serious AEs that were not listed on drug labels such as cefaclor-induced stupor (ten cases) and cefaclor-induced respiratory depression (four cases) were found. Detecting signals using a national pharmacovigilance database is useful for identifying unknown ADRs. This study identified signals of cephalosporins that warrant further investigation.
PubMed: 34063258
DOI: 10.3390/ph14050425 -
The Journal of Antibiotics Aug 1975Cefatrizine (SK&F 60771), a new orally-active semisynthetic cephalosporin antibiotic with broad-spectrum antibacterial activity, was compared with cephalexin and... (Comparative Study)
Comparative Study
Cefatrizine (SK&F 60771), a new orally-active semisynthetic cephalosporin antibiotic with broad-spectrum antibacterial activity, was compared with cephalexin and cefazolin for in vitro and in vivo antibacterial activity and pharmacokinetic behavior in laboratory animals. The average MIC values obtained with cefatrizine against gram-positive and gram-negative bacteria were superior to those obtained with cephalexin and somewhat poorer than those of cefazolin. In addition, a large percentage of the enterobacter and enterococcus isolates were found to be susceptible. Cefatrizine had a longer biological half-life and a higher peak serum level than either cefazolin or cephalexin when administered parenterally or orally to mice at 20 mg/kg. It had striking in vivo protective activity in mice infected with Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Hemophilus influenzae, Proteus morganii or Staphylococcus aureus reflecting its superior pharmacokinetic profile in this animal species. A variable pharmacokinetic response between animal species was observed when cefatrizine was administered either orally or parenterally to dogs, squirrel monkeys or rabbits.
Topics: Administration, Oral; Animals; Cefazolin; Cephalexin; Cephalosporins; Dogs; Drug Evaluation, Preclinical; Escherichia coli; Haplorhini; Klebsiella pneumoniae; Male; Mice; Microbial Sensitivity Tests; Rabbits; Staphylococcus aureus; Triazoles
PubMed: 808525
DOI: 10.7164/antibiotics.28.594 -
Pharmaceutical Research Feb 1993A theoretical analysis for estimating the extent of intestinal peptide and peptide analogue absorption was developed on the basis of a mass balance approach that...
A theoretical analysis for estimating the extent of intestinal peptide and peptide analogue absorption was developed on the basis of a mass balance approach that incorporates convection, permeability, and reaction. The macroscopic mass balance analysis (MMBA) was extended to include chemical and enzymatic degradation. A microscopic mass balance analysis, a numerical approach, was also developed and the results compared to the MMBA. The mass balance equations for the fraction of a drug absorbed and reacted in the tube were derived from the general steady state mass balance in a tube: [formula: see text] where M is mass, z is the length of the tube, R is the tube radius, Pw is the intestinal wall permeability, kr is the reaction rate constant, C is the concentration of drug in the volume element over which the mass balance is taken, VL is the volume of the tube, and vz is the axial velocity of drug. The theory was first applied to the oral absorption of two tripeptide analogues, cefaclor (CCL) and cefatrizine (CZN), which degrade and dimerize in the intestine. Simulations using the mass balance equations, the experimental absorption parameters, and the literature stability rate constants yielded a mean estimated extent of CCL (250-mg dose) and CZN (1000-mg dose) absorption of 89 and 51%, respectively, which was similar to the mean extent of absorption reported in humans (90 and 50%). It was proposed previously that 15% of the CCL dose spontaneously degraded systematically; however, our simulations suggest that significant CCL degradation occurs (8 to 17%) presystemically in the intestinal lumen.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Cefaclor; Cefatrizine; Humans; Insulin; Intestinal Absorption; Models, Biological; Peptides; Permeability
PubMed: 8456076
DOI: 10.1023/a:1018999130076