Carumonam

Carumonam (AMA-1080; Ro 17-2301) is a sulfonated monocyclic β-Lactam Antibiotic, targeting to penicillin-binding protein (PBP). Carumonam exerts highly activity against Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus influenzae, while it weakly and even inactively inhibits Streptococcus pneumoniae and Staphylococcus aureus. Carumonam is resistant to beta-lactamase-mediated hydrolysis^[1]. IC50 & Target:Penicillin-binding protein, PBP^[1] In Vitro:Carumonam shows inhibition against Enterobacteriaceae isolates with MIC₉₀ values of 0.013-25 μg/mL, while it inhibits P. aeruginosa with a MIC₉₀ value of 12.5 μg/mL^[1].
Carumonam (0-400 μg/mL) has high affinity to binding PBP-3 in Enterobacteriaceae and P. aeruginosa with IC₅₀s as same with or smaller than the MICs^[1].
In Vivo:Carumonam (20 mg/kg; s.c. or i.m.; single dose) is easily absorbed and distributes in high concentrations in plasma, kidneys, liver and lungs in pharmacokinetic analysis in mice, rats, rabbits, dogs and cynomolgus monkeys^[2].
Animal: Five-week-old male Slc:ICR mice (20-25 g), 7-week-old male Jcl:SD rats (210-250 g), male New Zealand White rabbits (2.5-3.5 kg), male and female beagle dogs (10-15 kg), and female cynomolgus monkeys (2.8-3.7 kg). They are deprived of feed for 16 to 18 h before the antibiotic was administered; water was given ad libitum^[2].

Pharmacokinetic Analysis^[2]

Animal	Dose (mg/kg)	Route	Tmax (h)	Cmax (μg/mL)	AUC (μg·h/mL)	t1/2 (h)	CLp (mL/min/kg)
Mouse	2 mg/mL, 0.1 mL/10 g	s.c.	0.12	40.7	20.0	0.24	16.7
Rat	10 mg/mL, 0.2 mL/100 g	i.m.	0.18	37.9	23.9	0.28	14.0
Rabbit	40 mg/mL, 0.5 mL/kg	i.m.	0.36	44.9	66.6	0.73	5.0
Dog	100 mg/mL, 0.2 mL/kg	i.m.	0.36	36.3	61.1	1.10	5.5
Monkey	20 mg/mL/kg	i.m.	0.29	67.9	80.4	0.89	4.5