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Query: EC:2.6.1.2 (
alanine aminotransferase
)
26,722
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The toleration and safety profile of the azalide antibiotic, azithromycin, has been assessed in 3,995 patients aged 2-94 (mean, 36) years, comprising 1,644 females and 2,351 males. Patients with infections of the respiratory tract or skin/skin structure received 1.5 g azithromycin over 5 days; patients with urethritis/cervicitis caused by Chlamydia were treated with 1 g as a single dose. Assessments of side effects and laboratory safety test abnormalities were made pretreatment and approximately 7-14 and 30 days after the start of therapy. Twelve standard antibiotics have been used for comparison. Overall, side effects were recorded in 12.0% of patients, significantly less (p less than 0.05) than with comparative drugs (14.2%). The most common side effects were diarrhea (3.6%), abdominal pain (2.5%), and other gastrointestinal symptoms. Ninety-three percent of side effects were classed as mild or moderate, and only 0.7% of patients withdrew from treatment, significantly less (p less than 0.001) than with comparative agents (2.6%). The frequency of side effects was not affected by patient age.
Azithromycin
had no marked or consistent effect on laboratory safety parameters. Treatment-related laboratory abnormalities were rare, the most common being transient increases of
ALT
and AST in 1.7% and 1.5% of patients, respectively. Specific tests revealed no neurologic, audiometric, or ophthalmologic abnormalities, or evidence of phospholipidosis. There were no pharmacokinetic interactions observed with theophylline, warfarin, cimetidine, carbamazepine, or methylprednisolone, but coadministration with food altered the absorption of the drug. Coadministration with antacids decreased the peak serum concentration of azithromycin, but did not affect its overall absorption.
Azithromycin
was well tolerated in the presence of a wide variety of concurrent illnesses and medications.
...
PMID:Clinical toleration and safety of azithromycin. 165 42
Azithromycin
(
AZM
) in 10% fine granules, a newly developed azalide antibiotic, was administered at a standard dose of 10 mg/kg once daily for 3 to 5 days (89.5% received 3 day administration) to children with infectious diseases and the efficacy and the safety of
AZM
were investigated. In addition
AZM
concentrations were determined in blood samples from 18 patients and in urine samples from 17 patients to examine o pharmacokinetic characteristics of
AZM
. 1. Absorption and excretion: Cmax's in 16 patients who received 10 mg/kg and 2 patients who received 20 mg/kg were 0.29 +/- 0.24 micrograms/ml and 0.75 micrograms/ml, respectively, while T 1/2's were 42.0 +/- 11.8 hours for the former and 51.3 hours for the latter. AUC(0 to approximately infinity)'s were 10.72 +/- 5.00 micrograms x hr/ml in the former and 28.83 micrograms x hr/ml in the latter. Urinary concentrations of
AZM
peaked at 48 to 72 hours after the administration of 10 mg/kg
AZM
in 14 patients, while it peaked at 24 to 48 hours in the patients who received 20 mg/kg. Urinary recovery rates in the first 120 hours after the start were 9.1 +/- 2.6% for 10 mg/kg and 10.8 +/- 3.4% for 20mg/kg. 2. Clinical efficacy: The study received 619 entries and 564 cases were evaluated for drug efficacy. The remaining were not evaluated because of dropout or exclusion. The efficacy rate, combining both "Excellent" and "Good" cases was 94.3% in 246 cases where pathogens were identified, classified as Group A. The efficacy rate was 90.7% for the remaining 321 cases, classified as Group B, where causative pathogens were unidentified. The difference between the two groups was no statistical significance. The combined efficacy rate was 92.2%. For the 116 cases where the patients had failed to respond to previous chemotherapies instituted for 3 days or longer, the efficacy rate for
AZM
was 94.0%. 3. Adverse reactions and abnormal laboratory tests: Incidents of diarrhea, soft stool, skin rashes, or vomiting were found in 15 patients (2.5%) of 596 cases eligible for evaluation. These reactions, however, were all transient and mild to moderate in severity in the 15 patients including 4 patients for whom the treatment was discontinued, all resolved in time. Abnormal changes in laboratory tests were found as follows: decrease in WBC in 23 patients (5.6%), increase in eosinophils in 28 (7.1%), increase in platelet count in 2 (0.5%), decrease in platelet count in 1 (0.3%), elevation of GOT in 3 (0.8%), and elevation of
GPT
in 6 (1.6%).(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:[Pharmacokinetic and clinical studies with azithromycin (fine granule) in the pediatric field. Pediatric Study Group of Azithromycin]. 747 29
Azithromycin
(
AZM
) in 100 mg capsules, a newly developed azalide antibiotic, was administered at a standard dose of 10 mg/kg once daily for 3 to 5 days (89.9% received 3 day administration) to children with infectious diseases and the efficacy and the safety of
AZM
were investigated. In addition,
AZM
concentrations were determined in blood samples from 9 patients and in urine samples from 12 patients to examine pharmacokinetic characteristics of
AZM
. 1. Absorption and excretion: Cmax was 0.45 +/- 0.28 micrograms/ml, T 1/2 was 52.7 +/- 20.2 hours, and AUC(0 approximately to infinity) was 12.09 +/- 4.93 micrograms.hr/ml in the 9 patients each of whom received 8.5 to 14.3 mg/kg
AZM
. Urinary concentrations of
AZM
peaked at 48 to 72 hours after the administration of 8.5 to 14.7 mg/kg
AZM
in 12 patients and the average urinary recovery rate in 120 hours was 7.3 +/- 2.8%. 2. Clinical efficacy: The study received 139 entries and 119 cases were evaluated for drug efficacy. The remaining were not evaluated because of dropout or exclusion. The efficacy rate combining both "Excellent" and "Good" cases, was 100% for 40 cases in which pathogens were identified, classified as Group A. The efficacy rate was 97.5% for the remaining 79 cases, classified as Group B, where causative pathogens were unidentified. The difference between the two groups was no statistical significance. The combined efficacy rate was 98.3%. For the 31 cases where the patients had failed to respond to the previous chemotherapies instituted for 3 days or longer, the efficacy rate for
AZM
was 93.5%. 3. Adverse reactions and abnormal laboratory tests: 8 incidents of diarrhea, skin rashes, urticaria, or vomiting were found in 7 patients (5.4%) of 130 cases eligible for evaluation. These reactions, however, were all transient and mild to moderate in severity in the 7 patients including 2 patients for whom the treatment was discontinued, all resolved in time. Abnormal changes in laboratory tests were found as follows: decrease in WBC in 10 patients (9.3%), an increase in eosinophils in 12 (11.4%), an increase in platelet count in 1 (1.0%), an elevation of GOT in 3 (3.1%), an elevation of
GPT
in 6 (6.2%), and an elevation of LDH in 1 (1.1%). The abnormalities were transient and did not require particular intervention. Moreover, none of the patients indicated clinical signs associated with the abnormal changes of laboratory tests.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Pharmacokinetic and clinical studies with azithromycin (capsule) in the pediatric field. Pediatric Study Group of Azithromycin]. 747 30
Azithromycin
(
AZM
), a new macrolide antibiotic, in fine granules and in capsules was studied for pharmacokinetic and clinical evaluation in the pediatric patients. Antibacterial activity of
AZM
against 43 clinical isolates:
AZM
exhibited slightly lower activity against Gram-positive bacteria and 2-8-fold higher activity against Gram-negative bacteria than erythromycin or clarithromycin. Plasma or urine samples were collected from eight patients receiving the drug in fine granular form, and two patients receiving it in capsules for the determination of drug levels. The elimination half-lives of
AZM
after administration at dose of 10 mg/kg/day for 3 days were 50.0 and 51.2 hours for fine granules, and 41.5 hours for capsules. AUC0-infinity was 11.7 and 24.3 micrograms.hr/ml for fine granules, and 8.3 micrograms.hr/ml for capsules. The cumulative excretion rates up to 120 hours after the start of treatment were 8.24 and 13.84% for fine granules, and 3.83% for capsules.
AZM
was administered to 123 patients once daily at 3.7-20.0 mg/kg body weight over 3 to 5 days with reference to the standard dose of 10 mg/kg. The drug was used to treat patients with pharyngitis, tonsillitis, scarlet fever, pneumonia, mycoplasmal pneumonia, chlamydial pneumonia, otitis media, pertussis, intestinal infection, and SSTI. The effectiveness of
AZM
was evaluated in 109 cases. The drug was rated "excellent" in 65.1% of the patients and "good" in 29.4%, resulting in an efficacy rate of 94.5%. Furthermore,
AZM
eradicated 43 of 46 (93.5%) bacteria that had been identified before the treatment. Three patients complained of side effects of urticaria (1 case) and diarrhea (2 cases). Abnormal laboratory changes were reported as follows: decreased leukocyte (3 cases), increased eosinophil (5), increased platelet (2), increased eosinophil and platelet, elevated
GPT
(1), and elevated GOT and
GPT
(1). The abnormalities, however, were mild enough to raise no clinically significant problems. In conclusion,
AZM
in once daily regimen was effective and safe in treatment of pediatric infections.
...
PMID:[Bacteriological, pharmacokinetic and clinical evaluation of azithromycin in the pediatric field]. 898 53
Azithromycin
(
AZM
), a new macrolide antibiotic, in fine granules and in capsules was studied for pharmacokinetic and clinical evaluations. 1. Antibacterial activities. MIC profile of
AZM
was as follows: 0.78 approximately 1.56 micrograms/ml against Staphylococcus aureus, < or = 0.025 approximately 0.10 microgram/ml against Streptococcus pyogenes, 0.10 approximately 0.39 and 6.25 micrograms/ml against Streptococcus pneumoniae, < or = 0.025 approximately 0.39 microgram/ml against Moraxella(Branhamella) catarrhalis, 0.39 approximately 3.13 micrograms/ml against Haemophilus influenzae, and 0.20 approximately 6.25 micrograms/ml against Haemophilus parainfluenzae. 2. Absorption and excretion. The elimination half-life of
AZM
after its administration at 10 mg/kg/day for three days was 28.1 approximately 46.1 hours. The cumulative urinary excretion rate in the first 120 hours after start of treatment was 4.01 approximately 8.47%. 3. Clinical evaluation.
AZM
was given to 76 pediatric patients to treat following infections: pharyngitis in seven, tonsillitis in 11, bronchitis in 11, pneumonia in 19, Mycoplasma pneumonia in eight, scarlet fever in 13, infective enteritis in one, SSTI in four, and otitis media in two. Effectiveness of
AZM
was assessed in 75 patients and the drug was rated "excellent" or "good" in 71 resulting in an efficacy rate of 94.7%, 87.0% of the 46 cases indicated that
AZM
had eradicated bacteria identified before the treatment. One patient complained of moderate diarrhea which disappeared after treatment of anti-diarrheic. Abnormal laboratory changes were reported in 12 patients in the following: decreased leukocytes in eight, increased eosinophils in two, increased platelet count in one, and increased
GPT
in one. All cases of abnormality was deemed mild in severity and clinically insignificant.
...
PMID:[Pharmacokinetic and clinical evaluation of azithromycin using fine granules or capsules in the pediatric patients]. 898 10
Azithromycin
(
AZM
) in fine granules was studied for its pharmacokinetics and clinical efficacies in eight child patients with ages between 1 month and 8 years. Informed consent was received from all of their parents.
AZM
was administered to the patients once a day at a dose of 10 mg/kg for 3 days. The clinical efficacies of
AZM
in 8 patients with microbial infections (pneumonia in one, Mycoplasma pneumonia in two, acute tonsillitis in one, pertussis in one, Campylobacter enteritis in one, infectious enteritis in one, Salmonella enteritis in one) were evaluated as "excellent" in five cases, "good" in two and "not evaluable" in one. As for the microbial efficacy, isolated strains were eradicated in 2 out of 3 patients. No adverse reaction was found except for one case with abnormal laboratory change, that is mildly increased
GPT
value. Plasma samples were collected from 3 cases. The elimination half-life of
AZM
was 45.8 hours. AUC0-infinity was 12.6 micrograms.hr/ml. Urine sample was collected from one.
AZM
concentration in urine was 35.0 micrograms/ml during a period between 48 and 72 hours after the start of treatment.
...
PMID:[Pharmacokinetic, bacteriological and clinical studies on azithromycin in children]. 910 80
Azithromycin
(
AZM
), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections. The following results were obtained in our studies of
AZM
for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety. 1. MICs of
AZM
, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive cocci, MICs of
AZM
ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains). These MICs were similar to those of the other macrolides. Among Gram-negative bacilli, MICs of
AZM
were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp. (1 strain). These values were similar to or lower than those of the other macrolides. Against Mycoplasma pneumoniae, MICs of
AZM
were < or = 0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed tolerance to
AZM
at MIC 25 micrograms/ml. The other agents exhibited higher MIC than
AZM
against this organism. 2. Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination. The patients received
AZM
at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days. Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3. Urine samples were collected from four patients receiving fine granules and four patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules. Urinary excretion rates of
AZM
in three patients on capsules lied in a range between 4.69 and 10.17%. 4. Effectiveness of
AZM
in fine granules was evaluated in 128 patients having a total of 19 different infections.
AZM
was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1%. Effectiveness of
AZM
in capsular form was evaluated in 23 patients with five different infections.
AZM
was found "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of 100%. 5.
AZM
in fine granules eradicated 45 strains of 54 in 8 different bacteria.
AZM
in capsules eradicated 9 strains of 10 strains in 6 different bacteria. 6. As for adverse reactions, one patient complained of eruption, one vomiting, one loose stool, five diarrhea, when administered with fine granular form of
AZM
. One patient on
AZM
capsules experienced urticaria and vomiting. 7. As for abnormal laboratory changes, three patients were found with decreased WBC, seven with increased eosinophil, two with increased GOT and
GPT
, one with increased
GPT
. They were all on fine granular form of
AZM
. As far as abnormalities found in patients administered with
AZM
in capsular form, two showed decreased WBC, one decreased WBC along with increased eosinophil, and three increased eosinophil.
...
PMID:[Clinical study on azithromycin in 10% fine granules and 100mg capsules in the field of pediatrics]. 963 60
The efficacy of a newly developed macrolide antibiotic, azithromycin, for infections in the field of surgery, was investigated clinically by means of collaborative studies conducted in 17 major institutes and their affiliated hospitals throughout Japan. The following results were obtained. Clinical assessment:
Azithromycin
was administered at a dose of 250 mg or 500 mg once a day for 3 days. Clinical efficacy was evaluated in 170 patients. These subjects consisted of 81 with superficial purulent diseases, 12 with mastitis, 25 with periproctal abscess, 42 with superficial secondary infection due to trauma, burn and operative wound, 5 with cholecystitis or cholangitis, and 5 with other infections. The clinical efficacy rate was 96.3% (78/81) for superficial purulent diseases, 83.3% (10/12) for mastitis, 84.0%(21/25) for periproctal abscess, and 76.2%(32/42) for superficial secondary infection due to trauma, burn and operative wound. The overall clinical efficacy rate was 88.8%(151/170) respectively. The bacteriological eradication rate was 87.9%(116/132) for gram-positive bacteria, 85.0%(34/40) for gram-negative bacteria, and 100%(63/63) for anaerobic strains of casual bacteria, which were isolated from 140 patients. The overall bacteriological eradication rate was 90.6%(213/235) respectively. Adverse effects were observed in 6 of 170 patients in whom they were evaluated. They consisted of gastrointestinal symptoms in 5 patients and exanthema in 1. Abnormal changes in clinical laboratory test values were observed in 5 patients, and consisted of eosinophilia in 1, elevations of S-GOT and S-
GPT
in 1, elevations of S-GOT, S-
GPT
and gamma-GTP in 1, elevation of S-
GPT
in 1, and elevations of AL-P and gamma-GTP in 1. These results suggest that azithromycin is very useful for surgical infections in the field of surgery.
...
PMID:[Clinical studies of azithromycin, a new macrolide antibiotic, for infections in the field of surgery]. 1257 91
Azithromycin
is extensively used in children with community-acquired pneumonia (CAP). Currently, the intravenous azithromycin is used off-label in children partly due to lacking of pharmacokinetic data. Our objective was to evaluate the population pharmacokinetics (PPK) and optimize dose strategy in order to improve treatment in this distinctive population. This was a prospective, multicenter, open-labeled pharmacokinetic study. Blood samples were collected from hospitalized pediatric patients and concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PPK analysis was conducted using NONMEM software. The pharmacokinetic data from 95 pediatric patients (age range, 2.1 to 11.7 years) were available for analysis. The PPK was best fitted by a two-compartment model with linear elimination. Covariate analysis verified that body weight and
alanine aminotransferase
(
ALT
) had significant effects on azithromycin pharmacokinetics, yielding a 24% decrease of clearance in patients with
ALT
of >40. Monte Carlo simulation showed that for children with normal liver function, a loading-dose strategy (a loading dose of 15 mg/kg of body weight followed by maintenance doses of 10 mg/kg) would achieve the ratio of the area under free drug plasma concentration-time curve over 24 h (
f
AUC) to MIC
90
(
f
AUC/MIC) target of 3 h in 53.2% of hypothetical patients, using a normative MIC susceptibility breakpoint of 2 mg/liter. For children with
ALT
of >40, the proposed dose needed to decrease by 15% to achieve comparable exposure. The corresponding risk of overdose for the recommended dosing regimen was less than 5.8%. In conclusion, the PPK of azithromycin was evaluated in children with CAP and an optimal dosing regimen was constructed based on developmental pharmacokinetic-pharmacodynamic modeling and simulation.
...
PMID:Population Pharmacokinetics and Dosing Optimization of Azithromycin in Children with Community-Acquired Pneumonia. 2994 52
