IDENTIFICATION AND USE: Streptomycin is aminoglycoside anti-bacterial agent. HUMAN EXPOSURE AND TOXICITY: Streptomycin has been replaced by gentamicin for most indications because the toxicity of gentamicin is primarily renal and reversible, whereas that of streptomycin is vestibular and irreversible. The administration of streptomycin may produce dysfunction of the optic nerve, including scotomas, presenting as enlargement of the blind spot. Among the less common toxic reactions to streptomycin is peripheral neuritis. This may be due either to accidental injection of a nerve during the course of parenteral therapy or to toxicity involving nerves remote from the site of antibiotic administration. Serious sensitivity reactions, such as anaphylaxis and dermatologic reactions including exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, angioedema, and Stevens-Johnson syndrome, have been reported rarely in patients receiving aminoglycosides; fatalities have occurred rarely. Cross-sensitivity occurs among the aminoglycosides. ANIMAL STUDIES: Clinical signs of toxicity in mice included restlessness, respiratory depression, loss of balance, unconsciousness, motor paralysis and coma following all routes of administration. Coma was more often associated with subcutaneous dosing. After oral dosing, restlessness and excessive thirst were observed, possibly due to an osmotic effect. Intravenous and subcutaneous administration of 30 to 70 mg/kg bw streptomycin to monkeys caused marked respiratory depression which sometimes necessitated artificial respiration. Intravenous injection of streptomycin at doses of 100 to 200 mg/lb bw (220-440 mg/kg bw) in dogs caused an irreversible depression of blood pressure. Respiration was stimulated by low but paralyzed by high (165 mg/kg bw) intravenous doses. A daily dose of streptomycin of 25-75 mg/lb bw/day (55-165 mg/kg bw/day) to cats caused progressive changes in posture and gait over about 20 days, including ataxia (of the hind legs first then fore-legs), and a progressive rotational nystagmus. Withdrawal of the drug resulted in a slow but complete recovery of vestibular function. Streptomycin was administered subcutaneously to 14 pregnant mice at 400 ug/kg bw/day on days 9, 10, and 11 of pregnancy. Twenty-eight mice used as controls were injected with water. The number of implants was reduced in treated mice (179 vs 351 in controls). Early deaths were higher in controls (3.9% in the streptomycin group vs 5.1% in controls).
Intravenous and intramuscular therapy with streptomycin has been linked to mild and asymptomatic elevations in serum alkaline phosphatase, but therapy rarely affects aminotransferase levels or bilirubin and changes typically resolve rapidly once streptomycin is stopped. Only isolated case reports of acute liver injury with jaundice have been associated with streptomycin therapy and always in combination with other antituberculosis medications which are more clearly hepatotoxic, such as isoniazid, pyrazinamide and rifampin. Streptomycin and the aminoglycosides are not mentioned in large case series of drug induced liver disease and acute liver failure; thus, hepatic injury from streptomycin must be exceedingly rare, if it occurs at all.
Due to poor oral absorption, aminoglycosides including streptomycin are administered parenterally. Streptomycin is available as an intramuscular injection, and in some cases may be administered intravenously. A peak serum concentration of 25-50 mcg/mL is achieved within 1 hour after intramuscular administration of 1 gram of streptomycin.
来源:DrugBank
吸收、分配和排泄
消除途径
大约50%的链霉素在静脉或肌肉注射后24小时内通过尿液排出。
Approximately 50% of streptomycin is eliminated in the urine within 24 hours after intravenous or intramuscular administration.
Following intramuscular injection of 1 g of streptomycin as the sulfate, a peak serum level of 25 to 50 ug/mL is reached within 1 hour, diminishing slowly to about 50 percent after 5 to 6 hours. Appreciable concentrations are found in all organ tissues except the brain. Significant amounts have been found in pleural fluid and tuberculous cavities. Streptomycin passes through the placenta with serum levels in the cord blood similar to maternal levels. Small amounts are excreted in milk, saliva, and sweat.
Streptomycin is rapidly absorbed after IM injection. Following IM administration of a single 1-g dose of streptomycin in adults with normal renal function, peak serum streptomycin concentrations are attained within 1 hour and range from 25-50 ug/mL; serum concentrations decrease 50% by 5-6 hours after the dose.
Comparative studies of androgen metabolism in theca and granulosa cells of human follicles in vitro
摘要：
In eight separate experiments, theca and granulosa were isolated from human follicles (5-25 mm in diameter), and their capacities to metabolize radiolabelled testosterone in 24 hour cultures were assessed. Theca metabolized testosterone primarily to androstenedione, however significant aromatization to estradiol-17 beta and to estrone was also observed. Granulosa metabolized testosterone primarily to estra-diol-17 beta and estrone, while smaller quantities were converted to androstenedione. In seven of these experiments, the intermediate of aromatization, 19-hydroxytestosterone, was identified. In six of these experiments, theca, when compared to granulosa, produced more androstenedione but less estradiol-17 beta and estrone. 5 alpha-Reduced androgens were non-detectable or produced in small quantities. In a single experiment, metabolism of androstenedione was compared to metabolism of testosterone by both theca and granulosa. Theca metabolized androstenedione to testosterone in smaller quantities than testosterone to androstenedione. Granulosa metabolized androstenedione to testosterone in higher quantities than testosterone to androstenedione. Both theca and granulosa aromatized androstenedione more readily than testosterone.
The invention relates to novel 3-amino pyrrolidine derivatives, as well as methods for modulating calcium channel activity and for treating conditions associated with calcium channel function. In particular, the compounds generally contain at least one benzhydril moiety, and are useful in treating conditions which benefit from blocking calcium ion channels.
[EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
申请人：GILEAD APOLLO LLC
公开号：WO2017075056A1
公开（公告）日：2017-05-04
The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
DISUBSTITUTED TRIFLUOROMETHYL PYRIMIDINONES AND THEIR USE
申请人：BAYER PHARMA AKTIENGESELLSCHAFT
公开号：US20160221965A1
公开（公告）日：2016-08-04
The present application relates to novel 2,5-disubstituted 6-(trifluoromethyl)pyrimidin-4(3H)-one derivatives, to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of cardiovascular, renal, inflammatory and fibrotic diseases.
NEW STRIGOLACTONE ANALOGUES AND THE USE THEREOF FOR THE TREATMENT OF PLANTS
申请人：INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE
公开号：US20150141255A1
公开（公告）日：2015-05-21
A compound of general formula (I):
in which X represents O, S, NH or an N-alkyl radical, R
1
and R
2
, identical or different, each represent H or a C
1
-C
10
hydrocarbon radical, R
1
and R
2
not both representing H, R
3
represents a C
1
-C
10
hydrocarbon radical, and R represents a phenyl radical monosubstituted or disubstituted by a substituent Y and, if applicable, a substituent Z, chosen from Cl, Br, I and CF
3
, or R represents a C═R
4
(R
5
) radical in which R
4
represents an hydrocarbon radical and R
5
represents a linear or branched, saturated or unsaturated, hydrocarbon radical, optionally substituted, a COR
6
group or a CO
2
R
6
group, where R
6
represents a hydrogen atom or a linear or branched, saturated or unsaturated, hydrocarbon radical. This compound can be used for the treatment of higher plants for controlling their growth and architecture.
Heterocyclic derivatives for the treatment of cancer and other proliferative diseases
申请人：——
公开号：US20020143182A1
公开（公告）日：2002-10-03
The invention relates to certain heterocyclic compounds useful for the treatment of cancer and other diseases, having the Formula (I):
1
wherein:
(a) m is an integer 0 or 1;
(b) R
12
is an alkyl, a substituted alkyl, a cycloalkyl, a substituted cycloalkyl, a heterocyclic, a substituted heterocyclic, a heteroaryl, a substituted heteroaryl, an aryl or a substituted aryl residue;
(c) Ar
3
is an aryl, a substituted aryl, a heteroaryl or a substituted heteroaryl residue;
(d) Ar
4
is an aryl, a substituted aryl, a heteroaryl or a substituted heteroaryl residue;
(e) R
5
is hydrogen, hydroxy, alkyl or substituted alkyl;
(f) - - - - - represents a bond present or absent; and
(g) W, X, Y and Z are independently or together C(O)—, C(S), S, O, or NH; or a pharmaceutically acceptable salt thereof.
