5,5′-Dimethyl-2,2′-bipyridine

184.24

184.24

6UO390AMFB

DTXSID00170095

29333990

25.8

2.2

1.060±0.06 g/cm3(Predicted)

114.5-115.0 °C @ Solvent: Ethanol

140℃/3mm

119.3±18.1 °C

1.566

0.000798mmHg at 25°C

NONH for all modes of transport

3

36/37/38-22

26-36

DW1766000

Xi,Xn

P261-P305 + P351 + P338

H302-H315-H319-H335

|Warning|H302 (88.37%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 43 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The intraperitoneal LD50 of abametapir in mice is 225 mg/kg. Topical formulations of abametapir contain benzyl alcohol, which has been associated with fatal reactions including "gasping syndrome" following systemic exposure in neonates and low birth weight infants. The use of benzyl alcohol-containing abametapir formulations should be avoided in patients <6 months of age due to an increased risk of unintentional systemic absorption. As benzyl alcohol toxicity may also occur in pediatric patients following accidental oral ingestion, the manufacturer recommends that it be administered to pediatric patients only under the direct supervision of adult. Symptoms of benzyl alcohol toxicity may include significant gastrointestinal and central nervous system adverse effects, with severe cases leading to respiratory depression and death. If toxicity is expected, patients should be advised to contact their nearest poison control center. The minimal amount of benzyl alcohol at which toxicity might occur is unclear. Toxicity is more likely in premature infants, low birth weight infants, and those receiving high doses.

Both abametapir and abametapir carboxyl are high protein-bound in plasma, although the specific proteins to which they bind are unclear. Following topical administration, abametapir is 91.3-92.3% protein-bound and abametapir carboxyl is 96.0-97.5% protein-bound.

Abametapir is indicated, in the context of an overall lice management program, for the topical treatment of head lice infestation in patients 6 months of age and older.

Abametavir has been shown to inhibit all stages of embryo development in both head and body lice by interfering with enzymes critical to this process. It is relatively unique amongst lice treatments in that it requires only a single application, whereas many current therapies require two applications, due to its exceptional potency and unique mechanism. Its predominant metabolite, abametapir carboxyl, has a prolonged residence time in the body, with an estimated half-life of 71 ± 40 hours or longer in adults - as this metabolite has been shown to inhibit cytochrome P450 enzymes _in vitro_, the use of substrates of CYP3A4, CYP2B6, or CYP1A2 should be avoided for two weeks following the administration of abametapir. Abametapir lotion is formulated with [benzyl alcohol], which has been associated with significant toxicity following unintentional systemic exposure, particularly in neonates and low birth weight infants. Benzyl alcohol-containing formulations should not be administered to patients <6 months of age, and should be administered to pediatric patients cautiously and under direct supervision of an adult to mitigate the risk of unintentional oral ingestion.

In a pharmacokinetic trial with both adult and pediatric patients, the C_max and AUC_0-8h in the adult group were 41 ng/mL and 121 ng.h/mL and the C_max and AUC_0-8h in the pediatric group were 73 ng/mL and 264 ng.h/mL. In general, systemic exposure to abametapir appears to decrease with increasing age. The median T_max of abemetapir is 0.57 - 1.54 hours. Following topical administration, benzyl alcohol was found in detectable quantities in the serum of 7 out of 39 pediatric patients. The C_max of benzyl alcohol in these subjects ranged from 0.52 to 3.57 μg/mL. The predominant circulating metabolite of abemetapir (abemtapir carboxylate) is eliminated slowly from the circulation and is therefore found at higher serum concentrations than its parent drug - based on data collected for 72 hours post-administration, the ratios of serum C_max and AUC_0-72h between abametapir and abametapir carboxylate were approximately 30 and 250, respectively.|The clearance and excretion of abametapir has not been examined in patients.|Data regarding the volume of distribution of abametapir are not available.

The biotransformation of abametapir is extensive and primarily mediated by CYP1A2. It is metabolized first to abametapir hydroxyl and then further to abametapir carboxyl - the latter is cleared slowly from the plasma, resulting in higher systemic concentrations than that of the parent drug. _In vitro_ studies suggest that abametapir carboxyl may act as an inhibitor of CYP3A4, CYP2B6, and CYP1A2, particularly at the relatively high and prolonged concentrations observed following topical administration of abametapir.

The elimination half-lives of abametapir and its metabolites have not been well-characterized, but the estimated half-life of abametapir carboxyl is 71 ± 40 hours (or longer) in adults.

There are several metalloproteinases (enzymes requiring metal co-factors to function) involved in the process of louse egg hatching and survival. _In vitro_ studies have demonstrated that metal-chelating agents can inhibit the activity of these proteins, and may therefore be valuable pediculicidal agents. Abametapir is a metalloproteinase inhibitor that targets louse metalloproteinases which are critical to their development and hatching.

5,5'-dimethyl-2,2'-bipyridyl

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients