Because abametapib can chelate heavy metal ions including iron, copper, and zinc, it can interact with a variety of insect targets, such as metalloproteinases, which need metal cofactors to operate [2].

Absorption, Distribution and Excretion
In a pharmacokinetic trial with both adult and pediatric patients, the Cmax and AUC0-8h in the adult group were 41 ng/mL and 121 ng.h/mL and the Cmax and AUC0-8h 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 Tmax 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 Cmax 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 Cmax and AUC0-72h 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 clearance and excretion of abametapir has not been examined in patients.

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Metabolism / Metabolites
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.

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Biological Half-Life
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.

Protein Binding
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.

[1]. Effect of a New Head Lice Treatment, Abametapir Lotion, 0.74%, on Louse Eggs: A Randomized, Double-Blind Study. Glob Pediatr Health. 2019; 6: 2333794X19831295.

[2]. Ovicidal Efficacy of Abametapir Against Eggs of Human Head and Body Lice (Anoplura: Pediculidae). J Med Entomol. 2017 Jan; 54(1): 167-172.

Abametapir is a member of bipyridines.
Abametapir is a novel pediculicidal metalloproteinase inhibitor used to treat infestations of head lice. The life cycle of head lice (Pediculus capitis) is approximately 30 days, seven to twelve of which are spent as eggs laid on hair shafts near the scalp. Topical pediculicides generally lack adequate ovicidal activity, including standard-of-care treatments such as [permethrin], and many require a second administration 7-10 days following the first to kill newly hatched lice that resisted the initial treatment. The necessity for follow-up treatment may lead to challenges with patient adherence, and resistance to agents like permethrin and [pyrethrins]/[piperonyl butoxide] may be significant in some areas. Investigations into novel ovicidal treatments revealed that several metalloproteinase enzymes were critical to the egg hatching and survival of head lice, and these enzymes were therefore identified as a potential therapeutic target. Abemetapir is an inhibitor of these metalloproteinase enzymes, and the first topical pediculicide to take advantage of this novel target. The improved ovicidal activity (90-100% in vitro) of abemetapir allows for a single administration, in contrast to many other topical treatments, and its novel and relatively non-specific mechanism may help to curb the development of resistance to this agent. Abametapir was first approved for use in the United States under the brand name Xeglyze on July 27, 2020.
See also: Pediculicide (subclass of).

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Drug Indication
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.

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Mechanism of Action
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.

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Pharmacodynamics
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.

C12H12N2

184.242

184.1

C, 78.23; H, 6.57; N, 15.21

1762-34-1

1762-34-1

15664

White to off-white solidw powder

1.1±0.1 g/cm3

315.7±37.0 °C at 760 mmHg

114-117 °C(lit.)

119.3±18.1 °C

0.0±0.6 mmHg at 25°C

1.566

2.2

0

2

1

14

161

0

N1C([H])=C(C([H])([H])[H])C([H])=C([H])C=1C1C([H])=C([H])C(C([H])([H])[H])=C([H])N=1

PTRATZCAGVBFIQ-UHFFFAOYSA-N

InChI=1S/C12H12N2/c1-9-3-5-11(13-7-9)12-6-4-10(2)8-14-12/h3-8H,1-2H3

5,5'-dimethyl-2,2'-bipyridinyl

Xeglyze 6,6'-Bi-3-picoline HA-44 BRN-0123183HA44 BRN 0123183HA 44 BRN0123183 Abametapir

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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

DMSO : ~25 mg/mL (~135.69 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (13.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (13.57 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 25.0 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 3: ≥ 2.5 mg/mL (13.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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