β-lactamase

Sulopenem may be used to treat both simple and complex urinary tract infections as well as intra-abdominal infections, including those that are multidrug-resistant (MDR) and those caused by Gram-negative bacteria that produce extended-spectrum β-lactamase (ESBL) and are not susceptible to quinolones[1].
At a concentration of ≤1 μg/mL, sulopenem inhibits the growth of the majority of isolates of aerobic and anaerobic Gram-positive and Gram-negative bacteria, including methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (penicillin-susceptible and -resistant isolates), group A and B β-hemolytic streptococci, Listeria monocytogenes, Enterobacteriaceae, Haemophilus influenzae, and Moraxella catarrhalis, but not P. aeruginosa and Stenotrophomonas maltophilia[1].

In experimental systemic infections in mice, Sulopenem has better protective effects than Imipenem/Cilastatin. Sulopenem has a lower ED50 in an experimental mixed infection of Escherichia coli and Bacteroides fragilis in mice. Sulopenem is more effective than CZON or Cefotiam in treating experimental lung infections caused by Klebsiella pneumoniae in guinea pigs[3].

Safety Information
Prescribing information includes warnings about hypersensitivity reactions, Clostridium difficile-associated diarrhea (CDAD), and the possibility of exacerbating gout when used in patients with a known history of gout. Orlynvah is contraindicated in patients with a history of hypersensitivity to Orlynvah components (sulpenem and probenecid) or other β-lactam antibiotics, patients with a known blood disorder, patients with a known uric acid kidney stone, and patients currently taking ketorolac tromethamine. The most common side effects of Orlynvah are diarrhea, nausea, vaginal yeast infection, headache, and vomiting.

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Use during Pregnancy and Lactation
◉ Overview of Use during Lactation
There is currently no clinical information regarding the use of sulpenem during lactation. Its excretion in breast milk is likely similar to that of imipenem and meropenem, which have lower concentrations in breast milk and are not expected to have adverse effects on breastfed infants. Limited information suggests that daily administration of probenecid up to 2 grams by the mother, resulting in low concentrations in breast milk, is not expected to have any adverse effects on breastfed infants, especially those older than 2 months. There are reports that β-lactam antibiotics occasionally disrupt the infant's gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. Sulperam-probenecid is safe for breastfeeding women.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

[1]. In Vitro Activity of Sulopenem, an Oral Penem, Against Urinary Isolates of Escherichia coli. Antimicrob Agents Chemother. 2018 Dec 21;63(1):e01832-18.

[2]. In Vitro Antibacterial Activity and Beta-Lactamase Stability of CP-70,429 a New Penem Antibiotic. Antimicrob Agents Chemother. 1993 Jul;37(7):1547-51.

[3]. In Vitro and in Vivo Activities of Sulopenem Compared With Those of Imipenem and Cephalosporins. Jpn J Antibiot. 1996 Apr;49(4):303-23.

Sulopenam is being studied in the clinical trial NCT03357614 (sulopenem followed by sulopenem-ezaloxazine/probenecid versus ertapenem followed by ciprofloxacin for the treatment of complicated urinary tract infections in adults). Sulopenam is an injectable thiopenem antibiotic with broad-spectrum antibacterial activity against most Gram-positive and Gram-negative bacteria. Sulopenam is ineffective against Pseudomonas aeruginosa. Furthermore, the drug is quite stable against the hydrolytic activity of various β-lactamases. Sulopenam is a penem antibiotic. It is marketed as a combination of the prodrug [sulopenem-ezaloxazine] and [probenecid]. Disease or condition: Uncomplicated urinary tract infection (UUTI) refers to a bacterial infection of the bladder in women without any structural abnormalities in the female urinary system. Approximately half of all women will experience at least one UUTI in their lifetime.
Efficacy
The efficacy of Orlynvah was evaluated in two phase 3 randomized, double-blind, controlled clinical trials (Trial 1 and Trial 2), both of which enrolled adult women with urinary tract infections (UTIs). Orlynvah is administered twice daily, one tablet each time, for 5 days.
Trial 1 (NCT05584657) was a non-inferiority trial in which 2214 adult women with UTIs were randomized to receive treatment. Orlynvah showed efficacy against amoxicillin/clavulanate-sensitive pathogens, with an overall response rate (combined microbiological and clinical remission) of 62%, compared to 55% in the amoxicillin/clavulanate group. Trial 2 (NCT03354598) was a non-inferiority trial in which 1660 adult women with urinary tract infections (uUTIs) were randomized to receive treatment. Orlynvah demonstrated efficacy in patients infected with ciprofloxacin-resistant pathogens, with an overall response rate of 48%, compared to 33% in the ciprofloxacin group. A total of 1932 patients were enrolled in the two trials to receive Orlynvah treatment. Clinical trials evaluating Orlynvah for complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI) did not confirm its efficacy.

C12H15NO5S3

349.434

349.011

C, 41.25; H, 4.33; N, 4.01; O, 22.89; S, 27.52

120788-07-0

112294-81-2 (sodium);120788-07-0;

9950244

White to yellow solid powder

1.74g/cm3

693.1ºC at 760mmHg

373ºC

3.2E-22mmHg at 25°C

1.768

1.21

2

8

4

21

563

5

O=S1CCC(SC2SC3C(C(=O)N3C=2C(=O)O)C(O)C)C1

FLSUCZWOEMTFAQ-IIOOQZKLSA-N

InChI=1S/C12H15NO5S3/c1-5(14)7-9(15)13-8(11(16)17)12(20-10(7)13)19-6-2-3-21(18)4-6/h5-7,10,14H,2-4H2,1H3,(H,16,17)/t5-,6+,7+,10-,21?/m1/s1

(5R,6S)-6-((R)-1-hydroxyethyl)-3-(((3S)-1-oxidotetrahydrothiophen-3-yl)thio)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

CP-70,429; CP 70,429; Sulopenem; 120788-07-0; CP-70429; CP70,429; XX514BJ1XW; CP70,429; CP-70429; CP 70429; CP70429; Sulopenem.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~83.33 mg/mL (~238.46 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2:

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 (Please use freshly prepared in vivo formulations for optimal results.)