Co-trimoxazole is metabolized in the liver. Trimethoprim is metabolized to oxide and hydroxylated metabolites and sulfamethoxazole is principally N-acetylated and also conjugated with glucuronic acid. Both drugs are rapidly excreted in urine via glomerular filtration and tubular secretion. In adults with normal renal function, approximately 50-60% of a trimethoprim and 45-70% of a sulfamethoxazole oral dose are excreted in urine within 24 hours. Approximately 80% of the amount of trimethoprim and 20% of the amount of sulfamethoxazole recovered in urine are unchanged drug. In adults with normal renal function, urinary concentrations of active trimethoprim are approximately equal to those of active sulfamethoxazole. Urinary concentrations of both active drugs are decreased in patients with impaired renal function.
◉ Summary of Use during Lactation:With healthy, fullterm infants it appears acceptable to use sulfamethoxazole and trimethoprim during breastfeeding after the newborn period. The time of greatest risk for hemolysis in fullterm newborns without glucose-6-phosphate dehydrogenase (G6PD) deficiency might be as short as 8 days after birth. Until further data are accumulated, alternate agents should probably be used in jaundiced, ill, stressed or premature infants, because of the risk of bilirubin displacement and kernicterus. Sulfamethoxazole and trimethoprim should be avoided while breastfeeding a G6PD-deficient infant.
◉ Effects in Breastfed Infants:An extensive systematic review of the use of sulfonamides near term and during breastfeeding found no adverse reactions in infants. The authors concluded that use of sulfamethoxazole-trimethoprim during breastfeeding presents no risk of neonatal kernicterus.
A prospective, controlled study asked mothers who called an information service about adverse reactions experience by their breastfed infants. Of 12 women who took sulfamethoxazole and trimethoprim during breastfeeding (time postpartum and dosage not stated), none reported diarrhea, drowsiness or irritability in her infant. Two mothers reported poor feeding in their infants.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
◈ What is sulfamethoxazole and trimethoprim?
Sulfamethoxazole and trimethoprim are medications that are used to treat bacterial infections. These two medications are usually given together and sold under the brand names Bactrim® or Septra®. The combination of these antibiotics is used to treat a variety of infections, including urinary tract infections (UTIs).
◈ I take sulfamethoxazole/trimethoprim. Can it make it harder for me to get pregnant?
It is not known if sulfamethoxazole/trimethoprim can make it harder to get pregnant.
◈ I just found out I am pregnant. Should I stop taking sulfamethoxazole/trimethoprim?
Talk with your healthcare providers before making any changes to how you take your medication. The benefits of taking your medication may outweigh the risks of untreated illness. It is important to treat most infections during pregnancy. Untreated UTIs could lead to severe kidney infection for the person who is pregnant, preterm delivery (delivery before 37 weeks of pregnancy) and preeclampsia (dangerously high blood pressure).
◈ I am taking sulfamethoxazole/trimethoprim, but I would like to stop taking it before becoming pregnant. How long do these medications stay in my body?
People eliminate medication at different rates. In healthy adults, it takes up to 3 days, on average, for most of sulfamethoxazole/trimethoprim to be gone from the body.
◈ Does taking sulfamethoxazole/trimethoprim increase the chance for miscarriage?
Miscarriage can occur in any pregnancy. Two studies have found an association with the use of sulfamethoxazole/trimethoprim in the first trimester and with miscarriage. However, one of these studies did not consider other factors that may have contributed to the chance of miscarriage.
◈ Does taking sulfamethoxazole/trimethoprim increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. There are not many well controlled studies on the use of sulfamethoxazole only in human pregnancy. Sulfamethoxazole is part of a group of medications called sulfonamides. Some studies have suggested the use of sulfonamides during the first trimester may be associated with an increased chance for birth defects while other studies have not.Concern has also been raised with the use of trimethoprim in pregnancy. There have been studies involving several hundred individuals using this medication at any time in pregnancy. Some studies have not found an increased chance for birth defects. However, a few studies looking at trimethoprim used with a sulfonamide during the first trimester have found an increased chance for birth defects, including heart defects, neural tube defects (opening in the spine), cleft lip or palate, and urinary tract defects.Trimethoprim may lower the level of folic acid in your body. Folic acid is a B vitamin that helps the body make new healthy cells and may help reduce the chance of certain birth defects, like spina bifida, in the baby. It is recommended that people who are pregnant or planning a pregnancy consume between 400-800 micrograms of folic acid each day from foods or vitamin supplements. If sulfamethoxazole/trimethoprim is taken during the first trimester, your healthcare provider may suggest that you take more folic acid. You can talk with them about how much folic acid is right for you.Use of sulfamethoxazole and trimethoprim after the first trimester is not associated with a higher chance of birth defects in the baby. Overall, if there is an increased chance for birth defects with use of sulfamethoxazole/trimethoprim during pregnancy, it appears to be small.
◈ Could taking sulfamethoxazole/trimethoprim cause other pregnancy complications?
One study has suggested that individuals who take medications that may lower levels of folic acid are at a greater chance for pregnancy complications such as preeclampsia, placenta abruption (when the placenta breaks away from the wall of the uterus) and fetal growth restriction. Exposure to sulfamethoxazole/trimethoprim has been associated with preterm delivery and low birth weight. However, this medication is frequently used to treat UTIs, and people who are pregnant with UTIs are at a greater chance for some of the same complications. It is hard to determine whether it is the medication, the decrease in folic acid, the underlying infection, or other factors which are increasing the chance for these complications.
◈ Can I take sulfamethoxazole/trimethoprim in the 3rd trimester?
Some authors have recommended not taking sulfonamides such as sulfamethoxazole after 32 weeks of pregnancy. There is a theoretical concern that sulfonamide use near the end of pregnancy can increase the chance for severe jaundice (a problem with liver function) and related complications in the baby. Your healthcare provider can help to suggest a medication that is right for you.
◈ Does taking sulfamethoxazole/trimethoprim in pregnancy cause long-term problems in behavior or learning for the baby?
It is not known if sulfamethoxazole/trimethoprim can cause behavior or learning issues.
◈ Can I breastfeed while taking sulfamethoxazole/trimethoprim ?
Sulfamethoxazole and trimethoprim pass into breast milk in small amounts. There is some concern about taking sulfamethoxazole and trimethoprim while breastfeeding if the baby is born before 37 weeks of pregnancy, has severe jaundice, or a condition known as glucose-6- phosphate dehydrogenase deficiency (G6PD deficiency). However, it is not always necessary to stop breastfeeding while taking these medications. Be sure to talk to your healthcare provider about all your breastfeeding questions.
◈ I take sulfamethoxazole/trimethoprim. Can it make it harder for me to get my partner pregnant or increase the chance of birth defects?
The combination of sulfamethoxazole and trimethoprim was found to lower sperm production in males who were taking it continuously for one month. A lowered sperm count may affect the ability to conceive a pregnancy.There are no studies looking at chance for birth defects when the father or sperm donor takes sulfamethoxazole/trimethoprim. In general, exposures that fathers or sperm donors have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.
Concomitant administration of trimethoprim or trimethoprim/sulfamethoxazole with methotrexate may increase bone marrow suppression, probably as an additive antifolate effect.
/Oral/ antidiabetic agents, may be displaced from protein binding sites and/or their metabolism may be inhibited by some sulfonamides, resulting in increased or prolonged effects and/or toxicity; dosage adjustments may be necessary during and after sulfonamide therapy. /Sulfonamides/
Concurrent use of bone marrow depressants with sulfonamides may increase the leukopenic and/or thrombocytopenic effects; if concurrent use is required, close observation for myelotoxic effects should be considered. /Sulfonamides/
Co-trimoxazole is widely distributed into body tissues and fluids, including sputum, aqueous humor, middle ear fluid, prostatic fluid, vaginal fluid, bile, and cerebrospinal fluid; trimethoprim also distributes into bronchial secretions. Trimethoprim has a larger volume of distribution than does sulfamethoxazole. In adults, apparent volume of distribution of 100-120 and 12-18 l have been reported for trimethoprim and sulfamethoxazole, respectively. In patients with uninflamed meninges, trimethoprim and sulfamethoxazole concentrations in cerebrospinal fluid are about 50 and 40%, respectively, of concurrent serum concentrations of the drugs. Trimethoprim and sulfamethoxazole concentrations in middle ear fluid are approximately 75 and 20%, respectively, and in prostatic fluid are approximately 200 and 35%, respectively, of concurrent serum concentrations of the drugs.
After a single oral dose of the combined preparation, trimethoprim is absorbed more rapidly than sulfamethoxazole. The concurrent administration of the drugs appears to slow the absorption of sulfamethoxazole. Peak blood concentrations of trimethoprim ususally occur by 2 hours in most patients, while peak concentrations of sulfamethoxazole occur by 4 hours after a single oral dose.
Trimethoprim is rapidly distributed and concentrated in tissues, and about 40% is bound to plasma protein in the presence of sulfamethoxazole. The volume of distribution of trimethoprim is almost nine times that of sulfamethoxazole. The drug readily enters cerebrospinal fluid and sputum. High concentrations of each component of the mixture are also found in bile.
The pharmacokinetics of trimethoprim-sulfamethoxazole were studied in 12 healthy adult subjects receiving trimethoprim at 20 mg/kg of body weight per day and sulfamethoxazole at 100 mg/kg/day, which is the conventional dose for treating Pneumocystis carinii pneumonia. Daily doses were evenly divided and orally administered every 6 h for 3 days. Trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole concn in serum and urine were measured by HPLC. Five subjects withdrew from the study because of intolerable GI and CNS toxicities. In the seven subjects that completed the study, the mean maximum serum drug concn after the last dose were 13.6 + or - 2.0, 372 + or - 64, and 50.1 + or - 10.9 ug/ml for trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole, respectively. The mean half-lives were 13.6 + or - 3.5, 14.0 + or - 2.3, and 18.6 + or - 4.3 hr, respectively. Changes in absolute neutrophil count were significantly correlated with the minimum concn of trimethoprim and sulfamethoxazole in serum and trimethoprim area under the concn-time curve (for all three parameters, r2 = 0.6 and p < 0.05). These findings add to the evidence that serum drug concn in adults following the conventional dose of trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia are excessive and contribute to certain adverse reactions.
This article reviews the pharmacokinetics, clinical use, and adverse effects of trimethoprim/sulfamethoxazole in renally impaired patients. Renal dysfunction changes the pharmacokinetics of both component drugs. Trimethoprim and sulfamethoxazole disposition are not significantly altered until creatinine clearance is less than 30 ml/min, when sulfamethoxazole metabolites and trimethoprim accumulate and may lead to toxicity. Renal dysfunction, however, does not preclude the use of trimethoprim/sulfamethoxazole to treat susceptible infections, even when creatinine clearance is less than 15 ml/min. Adverse effects may occur more frequently in renally impaired patients but are not clearly related to increased serum concentrations of either drug. Guidelines for appropriate dosing and monitoring of trimethoprim/sulfamethoxazole therapy in these patients are presented.
[EN] NOVEL FULLY SYNTHETIC AND SEMISYNTHETIC PLEUROMUTILIN DERIVATIVES AS NEW ANTIBIOTICS AND THEIR PREPARATION<br/>[FR] NOUVEAUX DÉRIVÉS DE PLEUROMUTILINE ENTIÈREMENT SYNTHÉTIQUES ET SEMI-SYNTHÉTIQUES EN TANT QUE NOUVEAUX ANTIBIOTIQUES ET LEUR PRÉPARATION
申请人：UNIV YALE
公开号：WO2019191547A1
公开（公告）日：2019-10-03
The present invention is directed to novel pleuromutllin antibiotic compounds, intermediates which are useful for making these novel antibiotic compounds, methods of synthesizing these compounds and related methods and pharmaceutical compositions for treating pathogens» especially bacterial infections, including gram negative bacteria.
[EN] AN OSTEOADSORPTIVE FLUOROGENIC SUBSTRATE OF CATHEPSIN K FOR IMAGING OSTEOCLAST ACTIVITY AND MIGRATION<br/>[FR] SUBSTRAT FLUOROGÈNE OSTÉOADSORBANT DE CATHEPSINE K POUR L'IMAGERIE DE L'ACTIVITÉ ET DE LA MIGRATION DES OSTÉOCLASTES
申请人：UNIV CALIFORNIA
公开号：WO2019018238A1
公开（公告）日：2019-01-24
In certain embodiments osteoadsorptive fluorogenic substrates of cathepsin K (or other proteases) are provided. Utilizing a bisphosphonate targeting moiety, the fluorogenic substrates provide effective bone-targeted protease sensor(s). In certain embodiments the "probes" comprise cleavable fluorophore-quencher pair linked by a cathepsin K (or other protease) peptide substrate and tethered to a bisphosphonate. Unlike existing probes that are cleared within a few days in vivo, the probes described herein (e.g., OFS-1) allow for monitoring resorption over the course of longer time periods with a single dose.
[EN] TUNABLE PH-SENSITIVE LINKER FOR CONTROLLED DRUG RELEASE<br/>[FR] LIEUR SENSIBLE AU PH RÉGLABLE POUR LA LIBÉRATION CONTRÔLÉE DE MÉDICAMENTS
申请人：UNIV WASHINGTON STATE
公开号：WO2016028700A1
公开（公告）日：2016-02-25
A novel acid labile linker for targeted delivery and/or controlled release of agents is introduced herein. There is further disclosed a method of developing a therapeutic or diagnostic conjugate for targeted cell-specific delivery. More specifically, the invention is focused on linkers used to deliver anticancer agents to specific tumor cells.
The invention relates generally to the discovery of specific nucleotide polymorphisms in the KCNE2 gene and the association of these polymorphisms with antibiotic-induced LQTS. Related composition screening systems and diagnostic and prognostic assays are provided.
Gallium complexes of 3-hydroxy-4-pyrones to treat mycobacterial infections
申请人：——
公开号：US20020068761A1
公开（公告）日：2002-06-06
Methods are provided for the use of gallium complexes of 3-hydroxy-4-pyrones in the treatment or prevention of infections caused by a prokaryote of the genus Mycobacterium, including but not limited to those infections due to
M. tuberculosis
and
M leprae
. Methods are also provided for the treatment of immunocompromised patients infected by these and other mycobacteria species, including species (such as
M. avium, M. aurum
, and
M. smegmatis
) that are not pathogenic to immunocompetent individuals but may cause disease in immunocompromised patients.
