Ropivacaine undergoes extensive metabolism, primarily via CYP1A2-mediated aromatic hydroxylation to 3-OH-ropivacaine. The main metabolites excreted in the urine are the N-dealkylated metabolite (PPX) and 3-OH-ropivacaine. Other identified metabolites include 4-OH-ropivacaine, the 3-hydroxy-N-dealkylated (3-OH-PPX) and 4-hydroxy-N-dealkylated (4-OH-PPX) metabolites, and 2-hydroxy-methyl-ropivacaine (which has been identified but not quantified). Unbound PPX, 3-hydroxy-, and 4-hydroxy-ropivacaine have demonstrated pharmacological activity in animal models less than that of ropivacaine.
来源:DrugBank
代谢
ropivacaine已知的人体代谢物包括PPX和3-羟基-ropivacaine。
Ropivacaine has known human metabolites that include PPX and 3-hydroxy-ropivacaine.
Hepatic
Route of Elimination: Ropivacaine is extensively metabolized in the liver, predominantly by aromatic hydroxylation mediated by cytochrome P4501A to 3-hydroxy ropivacaine. After a single IV dose approximately 37% of the total dose is excreted in the urine as both free and conjugated 3-hydroxy ropivacaine. In total, 86% of the ropivacaine dose is excreted in the urine after intravenous administration of which only 1% relates to unchanged drug.
Half Life: Approximately 4.2 hours.
Local anesthetics such as Ropivacaine block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. Specifically, they block the sodium-channel and decrease chances of depolarization and consequent action potentials. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
Systemic exposure to excessive quantities of lidocaine mainly result in central nervous system (CNS) and cardiovascular effects. CNS effects may include CNS excitation(nervousness, tingling around the mouth) followed by depression. [Wikipedia]
◉ Summary of Use during Lactation:Ropivacaine passes into milk poorly and is not orally absorbed by breastfed infants. Infants appear not to be affected by the small amounts of drug in breastmilk.
Local anesthetics administered during labor and delivery with other anesthetics and analgesics have been reported by some to interfere with breastfeeding. However, this assessment is controversial and complex because of the many different combinations of drugs, dosages and patient populations studied as well as the variety of techniques used. Published data on the use of ropivacaine and fentanyl used during labor and delivery in a small number of women found little or no adverse effect on breastfeeding. Although not well studied specifically with ropivacaine, it appears that with good breastfeeding support, epidural local anesthetics with or without fentanyl or one of its derivatives has little or no adverse effect on breastfeeding success. Labor pain medication may delay the onset of lactation.
◉ Effects in Breastfed Infants:Twenty-five infants whose mothers received a combination of ropivacaine and fentanyl for patient-controlled epidural analgesia for pain associated with cesarean section had normal Apgar and Neurological and Adaptive Capacity scores. No adverse effects were noted in any of the infants.
◉ Effects on Lactation and Breastmilk:A prospective cohort study compared women who received no analgesia (n = 63) to women who received continuous epidural analgesia with fentanyl and either 0.08 or 0.2% ropivacaine (n = 13) or bupivacaine (n = 39) during labor and delivery. The total dosage of ropivacaine was 50 to 124 mg and the average total infusion time from start to delivery was 219 minutes. The study found no differences between the groups in breastfeeding effectiveness or infant neurobehavioral status at 8 to 12 hours postpartum or the number exclusively or partially breastfeeding at 4 weeks postpartum.
A randomized, prospective study compared mothers who received epidural labor analgesia with ropivacaine (n = 75) to mothers who did not receive labor analgesia (n = 49). In the treatment group, 3 mL of ropivacaine 0.125% was injected epidurally, followed in some mothers by an additional 12 mL. In all treated mothers, 5 mL per hour was then given as a continuous epidural infusion. Although serum prolactin concentrations were somewhat lower in the group who received ropivacaine, no difference was seen between the groups in time of lactation onset, number of women with extensive lactation, and the decrease in infant weight reduction.
A nonrandomized study at one Italian hospital compared primiparous mothers undergoing vaginal delivery who received epidural analgesia (n = 64) to those who did not (n = 64). Mothers who requested the epidural analgesia received an initial dose of 100 mcg of fentanyl diluted to 10 mL with saline. After the initial fentanyl, doses of 15 to 20 mL of 0.1% ropivacaine were administered, if needed; however, the number of women who received ropivacaine was not reported. The only difference between the groups of mothers was a longer duration of labor among the treated mothers. The quality of infant nursing was equal between the 2 groups of infants on several measures; however, more infants in the treated group breastfed for less than 30 minutes at the first feeding.
A national survey of women and their infants from late pregnancy through 12 months postpartum compared the time of lactogenesis II in mothers who did and did not receive pain medication during labor. Categories of medication were spinal or epidural only, spinal or epidural plus another medication, and other pain medication only. Women who received medications from any of the categories had about twice the risk of having delayed lactogenesis II (>72 hours) compared to women who received no labor pain medication.
A nonrandomized convenience sample of women who did (n = 209) or did not (n = 157) receive epidural analgesia during labor was analyzed to determine whether epidurals affected the onset of lactation. Although not standardized, the typical procedure used sufentanil 10 to 15 mg together with either ropivacaine 0.1% or levobupivacaine 0.0625% epidurally, supplemented by epidural boluses of ropivacaine 0.1% or levobupivacaine 0.0625% about every 2 hours. No difference was found in the time of lactation onset between the two groups. Although women in both groups stated they wished to breastfeed prior to delivery, exclusive breastfeeding at 20 days postpartum was less frequent in the women who received an epidural (43%) than in women who did not (57%).
A retrospective study in a Spanish public hospital compared the infants of mothers who received an epidural during labor that contained fentanyl and either bupivacaine or ropivacaine. Infants of mothers who received an epidural had a lower frequency of early breastfeeding.
A study in China compared an epidural infusion of ropivacaine 700 mcg/hour (n = 76) to sufentanil 1.75 mcg/hour plus ropivacaine 700 mcg/hour (n = 81) during normal vaginal delivery. The combined ropivacaine and sufentanil provided better pain control than ropivacaine alone. Onset of lactation was shorter and lactation adequacy (milk volume) was better in the combined group than in the ropivacaine-only group.
来源:Drugs and Lactation Database (LactMed)
毒理性
暴露途径
硬脊膜外。
硬脊膜外给药后的生物利用度为87%-98%。
Epidural.
Bioavailability is 87%-98% following epidural administration.
Ropivacaine pharmacokinetics are highly dependent on the dose, route of administration, and patient condition. Following epidural administration ropivacaine undergoes complete and biphasic absorption.
来源:DrugBank
吸收、分配和排泄
消除途径
经静脉给药后，给药剂量的86%的罗哌卡因以尿液形式排出，其中1%为未改变的原药。
Following intravenous administration, 86% of the administered dose of ropivacaine is excreted in the urine, 1% of which comprises unchanged parent drug.
来源:DrugBank
吸收、分配和排泄
分布容积
静脉输注后，罗哌卡因的稳态分布容积为41 ± 7升。罗哌卡因能够轻易穿过胎盘。
Following intravascular infusion, ropivacaine has a steady-state volume of distribution of 41 ± 7 liters. Ropivacaine is able to readily cross the placenta.
Following intravenous administration, ropivacaine has a mean plasma clearance of 387 ± 107 mL/min, an unbound plasma clearance of 7.2 ± 1.6 L/min, and a renal clearance of 1 mL/min.
[EN] PROCESS FOR PRODUCING OPTICALLY ACTIVE N-ALKYL-PIPERIDINE-2-CARBOXANILIDE [FR] PROCÉDÉ DE PRODUCTION DE N-ALKYL-PIPÉRIDINE-2-CARBOXANILIDE OPTIQUEMENT ACTIF
Process for obtainment of enantiomers of n-(2,6-dimethylphenyl) -1-propyl-2-piperidinocarboxamide process for obtainment of non-racemic mixtures between the enantiomers of n-(2,6-dimethylphenyl) -1-propyl-2- piperidinocarboxamide compound consisting of non-racemic mixtures of enantiomers of n-(2,6-dimethylphenyl) -1-propyl -2- piperidinocarboxamide pharmaceutical compositions consisting of non-racemic mixtures of enantiomers of n-(2,6-dimethylphenyl) -1-propyl -2-piperidiniocarboxamide
[EN] THERAPEUTIC ACRYLATES AS ENHANCED MEDICAL ADHESIVES<br/>[FR] ACRYLATES THÉRAPEUTIQUES UTILES EN TANT QU'ADHÉSIFS MÉDICAUX AMÉLIORÉS
申请人：UNIV CARNEGIE MELLON
公开号：WO2018052936A1
公开（公告）日：2018-03-22
Provided herein are therapeutic acrylate compounds useful as medical adhesives, comprising a therapeutic agent covalently linked to a methacrylate or cyanoacrylate moiety. Adhesive compositions and kits, such as liquid sutures and bone cement also are provided along with uses for the compositions.
The present invention relates to dendrimer synthesis. Specifically, the present invention relates to triazine scaffolds capable of click chemistry for one-step synthesis of functionalized dendrimers, and methods of making and using the same.
PHOSPHONIUM ION CHANNEL BLOCKERS AND METHODS FOR USE
申请人：Nocion Therapeutics, Inc.
公开号：US20210128589A1
公开（公告）日：2021-05-06
The invention provides compounds of Formula (I), or pharmaceutically acceptable salts thereof:
The compounds, compositions, methods and kits of the invention are useful for the treatment of pain, itch, and neurogenic inflammation.
[EN] HDAC6 INHIBITORS AND IMAGING AGENTS<br/>[FR] INHIBITEURS DE HDAC6 ET AGENTS D'IMAGERIE
申请人：MASSACHUSETTS GEN HOSPITAL
公开号：WO2018191360A1
公开（公告）日：2018-10-18
Provided herein are compounds useful for binding to one or more histone deacetylase enzymes (HDACs). The present application further provides radiolabeled compounds useful as a radiotracer for position emission tomography imaging of HDAC. Methods for prepared unlabeled and labeled compounds, diagnostic methods, and methods of treating diseases associated HDAC are also provided.
