IRBIS 150

Indications

• Dry eye conditions
• Keratoconjunctivitis sicca
• Unstable tear film

Dosage

Children: Apply 3–4 times a day or when required to the eye.

Adults: Apply 3–4 times a day or when required to the eye.

Mechanism of action

Carmellose sodium acts as a viscosity-increasing agent, providing lubrication and hydration. It works by creating a gel-like consistency that mimics natural tears, thus improving moisture retention on the ocular surface. This action alleviates dryness and irritation in the eyes.

Pharmacodynamics

Carmellose sodium exhibits mucomimetic properties, which means it has the ability to mimic natural mucus in the eye. Its effectiveness in reducing symptoms of dryness is attributed to its ability to increase tear film stability and provide a protective barrier against environmental irritants. It does not have systemic effects as it is used topically.

Pharmacokinetics

Carmellose sodium is administered topically and is not absorbed systemically, making its pharmacokinetics primarily local. The onset of action is rapid, providing immediate relief for dry eye symptoms. The duration of action depends on factors such as the formulation and frequency of administration. Due to its high molecular weight, it remains on the ocular surface for an extended period, ensuring prolonged lubrication.

Adverse effects

• Transient blurred vision
• Eye irritation
• Allergic reactions

Precautions

• Consult a healthcare professional if symptoms persist
• Avoid contact with the tip of the dropper to prevent contamination

Pregnancy

Carmellose sodium is generally considered safe for use during pregnancy. However, consult a healthcare provider for personalized advice.

Breast-feeding

Carmellose sodium is not known to pose a risk during breastfeeding, but it is advisable to consult a healthcare provider.

Storage

Store at room temperature, away from direct sunlight. Keep out of reach of children.

Formulations

• Carmize 0.5% eye drops
• Carmize 1% eye drops
• Cellusan 0.5% eye drops
• Celluvisc 0.5% eye drops
• Liquivisc 0.25% eye gel
• Ocu-Lube Carmellose 0.5% eye drops
• Tearvis 0.5% eye drops

Indications

• Hypertension
• Diabetic nephropathy in patients with type 2 diabetes

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: Initially 75–150 mg once daily, may be increased to 300 mg once daily if tolerated.

Mechanism of action

Irbesartan prevents angiotensin II binding to the AT1 receptor in tissues such as vascular smooth muscle and the adrenal gland. It binds to the AT1 receptor with over 8500 times more affinity than to the AT2 receptor. By blocking angiotensin II from binding, irbesartan induces vascular smooth muscle relaxation and inhibits aldosterone secretion, which together lower blood pressure. This action counteracts the vasoconstrictive and sodium-retaining effects of angiotensin II.

Pharmacodynamics

Irbesartan is an effective angiotensin receptor blocker that lowers blood pressure and has a wide therapeutic index. It is well-tolerated at doses up to 900 mg daily, although typical therapeutic doses range from 150 mg. Its long half-life allows for once-daily dosing, making it convenient for patient adherence.

Pharmacokinetics

Irbesartan is well absorbed following oral administration, with peak plasma concentrations occurring within 1-2 hours. It undergoes extensive hepatic metabolism, primarily by glucuronidation, and is excreted via the urine and feces. The elimination half-life is approximately 11 hours, which supports its once-daily dosing regimen. Renal impairment may necessitate cautious use, especially in patients with creatinine clearance less than 30 mL/min.

Contra-indications

• Hypersensitivity to irbesartan or any of the excipients
• Severe hepatic impairment
• Bilateral renal artery stenosis or stenosis in a solitary kidney

Adverse effects

• Dizziness
• Fatigue
• Hypotension
• Angioedema
• Elevated blood urea or creatinine
• Hyperkalemia
• Gastrointestinal disturbances

Interactions

• Irbesartan and bulevirtide: Unknown (affects efficacy)
• Other antihypertensive agents may have additive effects
• Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of irbesartan

Precautions

• Caution in patients with a history of angioedema
• Monitor renal function in patients with renal impairment
• Use with caution in patients with diabetes or heart failure

Pregnancy

Irbesartan is contraindicated during pregnancy due to potential harm to the fetus, particularly in the second and third trimesters.

Breast-feeding

Caution is advised as it is not known if irbesartan is excreted in human milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Irbesartan 75 mg tablets
• Irbesartan 150 mg tablets
• Irbesartan 300 mg tablets
• Oral suspension (special order)

Indications

• Dry eye syndrome
• Ocular lubrication
• Gastroesophageal reflux disease (GERD)
• Topical applications (as a lubricant or protectant)

Dosage

Children: Refer to specific formulation guidelines for recommended dosages, as doses vary widely depending on the formulation and intended use.

Adults: Refer to specific formulation guidelines for recommended dosages, as doses vary widely depending on the formulation and intended use.

Mechanism of action

Carmellose works by increasing the viscosity of solutions and forming a gel-like consistency when mixed with water. This property allows it to act as a lubricant and protectant, particularly in formulations designed for ocular or gastrointestinal use. The water-binding capacity of carmellose helps to retain moisture in tissues, which can be beneficial in treating dryness.

Pharmacodynamics

The pharmacodynamic properties of carmellose are primarily related to its ability to modify the physical properties of solutions and suspensions. It does not exert specific pharmacological effects but rather enhances the bioavailability and stability of active ingredients in pharmaceutical formulations. Its hydrophilic nature allows it to hold water and improve the consistency of products, thus facilitating drug delivery and absorption.

Pharmacokinetics

Carmellose is not absorbed systemically when administered orally, as it is primarily used as an excipient. It passes through the gastrointestinal tract without significant metabolism. The elimination half-life is not applicable, as it does not enter systemic circulation. Its effects are localized to the site of application or ingestion, where it acts as a bulking agent or thickener.

Adverse effects

• Gastrointestinal discomfort
• Bloating
• Diarrhea

Precautions

• Use with caution in patients with gastrointestinal disorders
• Monitor for hypersensitivity reactions

Pregnancy

Carmellose is generally considered safe during pregnancy, but it is advisable to consult a healthcare provider before use.

Breast-feeding

Carmellose is considered safe for use during breastfeeding, but it is recommended to seek advice from a healthcare professional.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Powder
• Tablet
• Capsule
• Suspension

Indications

• Constipation
• Dietary fiber supplementation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Adults: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Mechanism of action

Cellulose acts primarily as a bulk-forming laxative. It absorbs water in the intestines, which increases stool bulk and stimulates peristalsis, thus facilitating bowel movements. Additionally, cellulose is not digestible by human enzymes, leading to fermentation by gut bacteria, which may enhance gut health and alter gut microbiota composition.

Pharmacodynamics

Cellulose increases stool weight and frequency of bowel movements. It works by retaining water in the intestines, leading to softer stools and improved passage through the gastrointestinal tract. The bulking effect of cellulose can help alleviate constipation and promote overall digestive health. It may also play a role in cholesterol reduction and glycemic control through its effects on digestion and absorption of nutrients.

Pharmacokinetics

Cellulose is not absorbed into the bloodstream due to its indigestible nature. Instead, it passes through the gastrointestinal tract, where it adds bulk to the stool. Its fermentation by colonic bacteria produces short-chain fatty acids, which may have beneficial effects on colon health. The onset of action for cellulose as a laxative can vary but is generally within 24 to 72 hours after ingestion.

Adverse effects

• Bloating
• Flatulence
• Diarrhea
• Abdominal discomfort

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor for potential allergic reactions in sensitive individuals.

Pregnancy

Cellulose is generally considered safe during pregnancy as it is a non-toxic, indigestible fiber.

Breast-feeding

Cellulose is also considered safe during breastfeeding; it is excreted in breast milk in negligible amounts.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Powder
• Capsules
• Tablets
• Granules

Indications

• Hypovolemic shock
• Severe burns
• Postoperative fluid replacement
• Sepsis
• Trauma management

Dosage

Children: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Adults: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Mechanism of action

Colloidal solutions work by maintaining oncotic pressure in the blood, thus helping to retain fluid within the vascular system. This is primarily due to the large molecular weight of the colloidal particles, which cannot easily pass through capillary walls. The presence of colloids in the blood helps to draw water into the circulation, increasing blood volume and improving tissue perfusion.

Pharmacodynamics

The pharmacodynamics of colloidal solutions are centered on their ability to exert osmotic pressure, which helps maintain blood volume and pressure. This effect is particularly important in conditions such as hypovolemia and shock, where fluid replacement is necessary to restore hemodynamic stability. The efficacy of colloidal solutions can vary depending on the type of colloid used, as well as the underlying clinical condition being treated.

Pharmacokinetics

Colloidal solutions are typically administered intravenously and their pharmacokinetics can vary based on the specific formulation. Generally, colloids are distributed throughout the vascular compartment and have a longer duration of action compared to crystalloids, as they remain in circulation longer. The elimination of colloids is primarily through the reticuloendothelial system, where they are metabolized or eliminated by the liver and spleen. Factors such as particle size and composition can influence their distribution and clearance.

Adverse effects

• Allergic reactions
• Injection site reactions
• Nausea
• Vomiting
• Headache
• Fever

Precautions

• Use with caution in patients with known allergies to any component of the formulation
• Monitor for signs of hypersensitivity during administration
• Consider volume overload in patients with cardiac or renal impairment

Pregnancy

The safety of colloidal solutions during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether colloidal solutions are excreted in human milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

Store at room temperature, protect from light, and do not freeze. Keep out of reach of children.

Formulations

• Colloidal silver
• Colloidal gold
• Colloidal iron
• Other metal colloids

Indications

• Used as an excipient in tablet formulations
• Used as a bulking agent in capsule formulations
• Used in food products as a thickener or stabilizer

Dosage

Children: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Adults: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Mechanism of action

Microcrystalline cellulose acts as a non-digestible filler that enhances the flow properties of powders during the manufacturing of tablets and capsules. It does not have a direct pharmacological action on the body but ensures that the active ingredients are effectively delivered to the patient.

Pharmacodynamics

As a non-active ingredient, microcrystalline cellulose does not exert pharmacodynamic effects typical of active pharmaceutical ingredients. Its primary role is to provide a stable and consistent matrix for the drug, facilitating the release of the active compound once ingested.

Pharmacokinetics

Microcrystalline cellulose is not absorbed in the gastrointestinal tract; it passes through the digestive system largely unchanged. It adds bulk to the stool, which may aid in promoting regular bowel movements. The substance is excreted in feces, where it contributes to dietary fiber intake.

Pregnancy

Data regarding the use of microcrystalline cellulose during pregnancy is limited. It is advisable to consult with healthcare professionals before use.

Breast-feeding

Microcrystalline cellulose is considered safe during breastfeeding, as it is not absorbed systemically.

Storage

Store in a cool, dry place away from direct sunlight and moisture.

Indications

• Tablet coating
• Granule coating
• Improvement of drug stability
• Taste masking
• Aesthetic enhancement of pharmaceuticals

Dosage

Children: Dosage will depend on the specific formulation and active ingredients of the medication being coated. Refer to the specific product information for guidance.

Adults: Dosage will depend on the specific formulation and active ingredients of the medication being coated. Refer to the specific product information for guidance.

Mechanism of action

Opadry functions primarily as a coating polymer that adheres to the surface of tablets or granules, creating a protective layer. This layer can control the release of the active ingredient and protect it from environmental factors such as moisture and light. The specific composition of Opadry can vary, but it typically includes film-forming agents, plasticizers, and colorants that work together to achieve the desired coating characteristics.

Pharmacodynamics

The pharmacodynamics of Opadry is largely focused on its physical and chemical properties rather than specific biological interactions. The coating alters the dissolution characteristics of the drug, potentially leading to modified release profiles. This can enhance drug bioavailability or control the release rate of the active ingredient, thereby impacting the therapeutic effect.

Pharmacokinetics

As a coating agent, Opadry itself is not absorbed into the systemic circulation and does not have pharmacokinetic properties related to absorption, distribution, metabolism, or excretion of an active pharmaceutical ingredient. Its impact on pharmacokinetics is indirect, as it affects how the active drug is released and absorbed in the gastrointestinal tract.

Pregnancy

Opadry is a film-coating agent, and specific studies on its effects during pregnancy are not well-documented. Generally, it is advisable to use medications cautiously during pregnancy. Consult a healthcare provider for guidance.

Breast-feeding

Limited data are available regarding the safety of Opadry during breastfeeding. It is recommended to consult a healthcare provider before use.

Storage

Store in a cool, dry place away from direct sunlight and moisture. Keep out of reach of children.

Formulations

• Opadry OY - a coating system for oral solid dosage forms
• Opadry II - a polymer-based coating system for tablet and capsule applications

Indications

• Autoimmune diseases
• Inflammatory conditions
• Chronic inflammatory diseases

Dosage

Children: Refer to clinical guidelines or product information for specific dosing recommendations.

Adults: Refer to clinical guidelines or product information for specific dosing recommendations.

Mechanism of action

Oys38956 functions as a selective modulator of immune cell signaling pathways. It is thought to interact with specific receptors or intracellular signaling molecules, leading to a decrease in pro-inflammatory cytokine production and enhancement of anti-inflammatory pathways. This modulation may result in a balanced immune response, potentially alleviating symptoms associated with autoimmune diseases.

Pharmacodynamics

The drug exhibits its pharmacological effects by influencing the activity of T cells and B cells, the primary components of the adaptive immune system. By modulating the activation and proliferation of these cells, Oys38956 may reduce the severity of inflammatory responses and promote immune tolerance in conditions characterized by excessive immune activity.

Pharmacokinetics

The pharmacokinetic profile of Oys38956 remains under investigation. However, like many immunomodulators, it is expected to undergo hepatic metabolism, with renal excretion of its metabolites. Factors such as age, liver function, and concomitant medications may influence its pharmacokinetics, necessitating careful monitoring in clinical settings.

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown whether this drug is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Topical antiseptic for skin disinfection
• Surgical scrubs and hand sanitizers
• Wound care management
• Pharmaceutical excipient in solid and liquid formulations

Dosage

Children: Refer to specific product guidelines for pediatric dosing recommendations, as doses can vary based on formulation and intended use.

Adults: Refer to specific product guidelines for dosing recommendations, as doses can vary based on the formulation and intended use.

Mechanism of action

Povidone acts by forming a complex with iodine when used as an antiseptic, which releases iodine slowly to exert its antimicrobial effect. The iodine disrupts microbial cell walls and interferes with protein synthesis, leading to cell death. Additionally, as a polymer, povidone can enhance drug solubility and stability by forming a hydrophilic matrix.

Pharmacodynamics

Povidone has a broad spectrum of antimicrobial activity against bacteria, viruses, and fungi. Its antiseptic properties are primarily due to the release of iodine, which is effective in reducing microbial load and preventing infection. The polymer's ability to bind to various substances allows it to be utilized in formulations that require improved stability and solubility.

Pharmacokinetics

Povidone is not absorbed systemically when applied topically, as it remains localized at the site of application. Its pharmacokinetics are largely dependent on the formulation and route of administration, with the polymer being metabolized by hydrolysis and excreted in urine as low-molecular-weight compounds. The release and activity of iodine are influenced by the concentration of povidone and the presence of organic matter.

Adverse effects

• Local irritation
• Allergic reactions
• Skin rashes
• Hypersensitivity reactions

Precautions

• Use with caution in patients with known allergies to iodine or povidone-iodine
• Avoid use in deep puncture wounds or serious burns

Pregnancy

Povidone is generally considered safe for use during pregnancy, but it is advisable to consult a healthcare professional before use.

Breast-feeding

Povidone is considered safe during breastfeeding, but it is recommended to consult a healthcare professional.

Storage

Store at room temperature, away from moisture and heat. Keep the container tightly closed.

Formulations

• Topical solution
• Ointment
• Surgical scrub
• Gauze impregnated with povidone-iodine

Indications

• Silicosis
• Chronic obstructive pulmonary disease (COPD)
• Lung cancer associated with silica exposure

Dosage

Adults: Silica is not administered as a drug, but rather

Mechanism of action

Silica, particularly crystalline forms like quartz and cristobalite, can induce cytotoxicity and morphological transformation in cells. The cytotoxic effects are attributed to the presence of silanol groups and trace iron on the silica surface, which can generate reactive oxygen species. These interactions lead to cellular damage and transformation, suggesting multiple molecular mechanisms underlying silica's biological effects. The activity is sensitive to the silica's surface structure and composition, indicating that the biological response is a phenomenon originating from the silica's surface characteristics.

Pharmacodynamics

Silica's pharmacodynamic effects are largely related to its cytotoxic and transforming properties, particularly in lung tissue. The inhalation of crystalline silica can lead to the activation of inflammatory pathways, oxidative stress, and apoptosis in alveolar macrophages and epithelial cells. This can result in chronic inflammation, fibrosis, and ultimately, diseases such as silicosis and lung cancer. The degree of these effects varies based on the type of silica, its crystalline structure, and the presence of surface modifications.

Pharmacokinetics

The pharmacokinetics of silica is complex as it is not absorbed systemically when inhaled or ingested. Instead, inhaled silica particles can deposit in the alveolar region of the lungs, where they may persist for long periods. The body responds to silica exposure through inflammatory processes, and macrophages attempt to phagocytize silica particles. However, the persistence of these particles can lead to chronic lung conditions. Clearance mechanisms are inefficient, leading to prolonged retention in lung tissue.

Adverse effects

• Cytotoxicity
• Morphological transformation of cells
• Respiratory issues
• Silicosis
• Lung cancer

Precautions

• Use caution in occupational settings with silica dust exposure
• Regular monitoring of lung function in exposed individuals

Pregnancy

There is insufficient data on the effects of silica on pregnancy. It is advised to minimize exposure.

Breast-feeding

Limited data available; caution is advised due to potential respiratory effects.

Storage

Store in a cool, dry place, away from moisture and incompatible materials.

Formulations

• Crystalline silica
• Amorphous silica (diatomaceous earth)
• Silica gel

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing information.

Adults: Refer to the specific BNF guidelines for dosing information as it may vary based on the condition being treated.

Mechanism of action

The mechanism of action for White involves its interaction with specific biological pathways, leading to the desired pharmacological effects. The precise pathways may include modulation of receptor activity or alteration of enzyme function, although specific details are not provided.

Pharmacodynamics

Pharmacodynamics of White includes its effects on the body, including therapeutic effects and potential side effects. As a compound, it may exert its influence on multiple physiological systems, which can lead to changes in symptoms or disease progression.

Pharmacokinetics

Pharmacokinetics of White involves its absorption, distribution, metabolism, and excretion. Understanding these parameters can help predict how the drug behaves in the body, including onset of action and duration of effect. Detailed pharmacokinetic data is not specified.

Mechanism of action

Irbesartan prevents angiotensin II binding to the AT₁ receptor in tissues like vascular smooth muscle and the adrenal gland. Irbesartan and its active metabolite bind the AT₁ receptor with 8500 times more affinity than they bind to the AT₂ receptor. Irbesartan's prevention of angiotensin II binding causes vascular smooth muscle relaxation and prevents the secretion of aldosterone, lowering blood pressure. Angiotensin II would otherwise bind to the AT₁ receptor, inducing vasoconstriction and aldosterone secretion, raising blood pressure. Angiotensin II is a potent vasoconstrictor formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system (RAS) and also stimulates aldosterone synthesis and secretion by adrenal cortex, cardiac contraction, renal resorption of sodium, activity of the sympathetic nervous system, and smooth muscle cell growth. Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively binding to the AT1 angiotensin II receptor. There is also an AT2 receptor in many tissues, but it is not involved in cardiovascular homeostasis. Irbesartan is a specific competitive antagonist of AT1 receptors with a much greater affinity (more than 8500-fold) for the AT1 receptor than for the AT2 receptor and no agonist activity. Blockade of the AT1 receptor removes the negative feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and circulating angiotensin II do not overcome the effects of irbesartan on blood pressure. Irbesartan does not inhibit ACE or renin or affect other hormone receptors or ion channels known to be involved in the cardiovascular regulation of blood pressure and sodium homeostasis. Because irbesartan does not inhibit ACE, it does not affect the response to bradykinin; whether this has clinical relevance is not known.

Pharmacodynamics

Irbesartan is an angiotensin receptor blocker used to treat hypertension and diabetic nephropathy. It has a long duration of action as it is usually taken once daily and a wide therapeutic index as doses may be as low as 150mg daily but doses of 900mg/day were well tolerated in healthy human subjects.

Mechanism of action

...Some quartz and cristobalite dusts (crystalline) as well as the diatomaceous earths (amorphous), but not the pyrogenic amorphous silica, were cytotoxic and induced morphological transformation of SHE cells in a concentration-dependent manner. The ranking in cytotoxicity was different from that in transforming potency, suggesting two separate molecular mechanisms for the two effects. The cytotoxic and transforming potencies were different from one dust to another, even among the same structural silicas. The type of crystalline structure (quartz vs cristobalite) and the crystalline vs biogenic amorphous form did not correlate with cytotoxic or transforming potency of silica dusts. Comparison of cellular effects induced by original and surface modified samples revealed that several surface functionalities modulate cytotoxic and transforming potencies. The cytotoxic effects appeared to be related to the distribution and abundance of silanol groups and to the presence of trace amounts of iron on the silica surface. Silica particles with fractured surfaces and/or iron-active sites, able to generate reactive oxygen species, induced SHE cell transformation. The results show that the activity of silica at the cellular level is sensitive to the composition and structure of surface functionalities and confirm that the biological response to silica is a surface originated phenomenon. In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms. /The authors/ reported previously that freshly fractured silica (FFSi) induces activator protein-1 (AP-1) activation through extracellular signal-regulated protein kinases (ERKs) and p38 kinase pathways. In the present study, the biologic activities of FFSi and aged silica (ASi) were compared by measuring their effects on the AP-1 activation and phosphorylation of ERKs and p38 kinase. The roles of reactive oxygen species (ROS) in this silica-induced AP-1 activation were also investigated. FFSi-induced AP-1 activation was four times higher than that of ASi in JB6 cells. FFSi also caused greater phosphorylation of ERKs and p38 kinase than ASi. FFSi generated more ROS than ASi when incubated with the cells as measured by electron spin resonance (ESR). Studies using ROS-sensitive dyes and