Absorption cutaneous

When a topically applied compound induces a biological response following skin absorption, the quantitation of that response may provide a basis for assessing skin absorption. Indeed, such physiological or pharmacological responses have been employed as endpoints in assessing skin absorption in vivo, and perhaps the most successful example is the vasoconstrictor response to topical corticosteroids. However, while these pharmacodynamic endpoints may be very sensitive and selective for defined classes of compounds, it should be noted that the parameter measured is the product of both the quantity and the potency of the compound under investigation and may not necessarily reflect the extent of skin absorption, cutaneous metabolism, or disposition. 

Duprez K, Bilweis J, Dupre A and Merle M (1988), Exf)erimental and clinical study of fast absorption cutaneous suture material , Ann de Chir de la Main, 7,91. 

Ceiling value and skin absorption special measures to prevent significant cutaneous absorption may be required. 

Skin" Notation-. The designation "skin" refers to the potential contribution to the overall exposure by the cutaneous route, including mucous membranes and eyes, either by airborne, or more particularly by direct, contact with the substance. Examples of such substances are phenol (cresol and cumene), hydrogen cyanide, and mercury. The "skin" notation is intended to make known the need to prevent cutaneous absorption so that the TLV is not violated. 

Cutaneous absorption of the neat material may occur, adding to the systemic toxicity. 

J. E. Riviere, K. F. Bowman, and N. A. Monteiro-Riviere. The isolated perfused porcine skin flap (IPPSF). I. A novel in vitro model for percutaneous absorption and cutaneous toxicology studies. Fundam. Appl. Toxicol. 7 444—453 (1986). 

Brooks JD, Riviere JE. 1996. Quantitative percutaneous absorption and cutaneous distribution of binary mixtures of phenol and para-nitrophenol in isolated perfused porcine skin. Fundam Appl Toxicol... 

Foxall PJD, Bending MR, Gartland KI, et al. 1989. Acute renal failure following accidental cutaneous absorption of phenol Application of NMR urinalysis to monitor the disease process. Human Toxicol 9 491-496. 

For in vitro testing the Organisation for Economic Cooperation and Development (OECD) approved in 2004 test guideline 428 [37], which currently advocates the use of human, rat, and pig skin to measure cutaneous absorption by a vertical diffusion system (Franz cell). Dmg concentrations are followed in an acceptor fluid separated by the skin from the donor vehicle, which is applied to the external surface of the skin. Instead of human or animal skin, human skin models could be used as soon as the equivalence of their results are proven. Comparative studies indicate a correlation of penetration data in vitro and in humans [38]. 

Permethrin, a synthetic pyreth-roid, exhibits similar anti-ectoparasitic activity and may be the drug of choice due to its slower cutaneous absorption, fast hydrolytic inactivation, and rapid renal elimination. 

In the occupational setting, inhalation is the most important route of entry of chemical agents into the body, followed by contact with skin and subsequent cutaneous absorption. Although the gastrointestinal tract is a potential site of absorption, the ingestion of significant amounts of chemicals is rare in the occupational setting. 

The stratum corneum plays a critical role in determining cutaneous permeability. Absorption is faster through skin that is abraded or inflamed. Chemicals that are not normally considered hazardous may be dangerous to individuals suffering from active inflammatory dermatoses. 

Green AlA A household remedy misused— fatal cresol poisoning following cutaneous absorption—(a case report). Med Sci Law 15 65-66, 1975... 

The approximate lethal dose for skin absorption in pregnant rats and rabbits was 7.5 and 5.0g/kg, respectively Cutaneous application of DAIAC resulted in a marked incidence of embryo mortality at doses that did not affect maternal body weight or produce any signs of maternal toxicity. Teratogenic effects (three fetuses from one dam with encephalocele one of eight with diffuse subcutaneous edema) were found in rats only when DMAC was applied on gestation days 10 and 11 at a total dose of 2400 mg/kg. In another study, DMAC administered... 

Contact with the eye by the gas or liquid resulted in transient irritation and conjunctivitis. Minor skin exposure to the liquid produced erythema and edema." Prolonged or repeated contact resulted in deeper burns with delayed vesiculation." It is doubtful that significant cutaneous absorption occurs. Although victims of skin exposure may show symptoms of neurotoxicity, inhalation is considered the likely cause."... 

Topical formulations of nystatin and of amphotericin B are useful in the management of Candida albicans infections of the skin. Both antibiotics are ineffective against dermatophytes. The use of nystatin is limited to topical treatment of cutaneous and mucosal Candida infections because of its narrow spectrum and its negligible absorption from the gastrointestinal tract. Hypersensitivity reactions are rare. It is not known whether topical nystatin can cause fetal harm when used by a pregnant woman. Amphotericin B has broader antifungal activity but its topical use is restricted to Candida. Topical use of amphotericin B has shown minimal absorption through the skin and is well tolerated. Limited human surveillance data do not indicate any harm to mother or fetus, but relative safety is still unknown. 

In general, ethanol in low to moderate amounts, is relatively benign to most body systems. A moderate amount of ethanol causes peripheral vasodilation, especially of cutaneous vessels, and stimulates the secretion of salivary and gastric fluids the latter action may aid digestion. On the other hand, ethanol consumption in high concentrations, as found in undiluted spirits, can induce hemorrhagic lesions in the duodenum, inhibit intestinal brush border enzymes, inhibit the uptake of amino acids, and limit the absorption of vitamins and minerals. In addition, ethanol can reduce blood testosterone levels, resulting in sexual dysfunction. 

Miconazole (Monistat) is a broad-spectrum imidazole antifungal agent used in the topical treatment of cutaneous dermatophyte infections and mucous membrane Candida infections, such as vaginitis. Minimal absorption occurs from skin or mucous membrane surfaces. Local irritation to skin and mucous membranes can occur with topical use headaches, urticaria, and abdominal cramping have been reported with treatment for vagiiutis. 

Good cutaneous absorption, prolonged skin retention, and fungicidal activity are potential advantages. Comparative trials with other agents necessary... 

Mechanism of Action A mast cell stabilizer that prevents increase in cutaneous vascular permeability, antigen-stimulated histamine release, and may prevent calcium influx into mast cells. Therapeutic Effect Inhibits sensitivity reaction. Pharmacokinetics Nondetectable absorption. Half-life 8.5 hr. 

Contraindications Hypersensitivity to pimecrolimus or any component of the formulation, Netherton s syndrome (potential for increased systemic absorption), application to active cutaneous viral infections. 

Numerous deaths due to ingestion, inhalation or cutaneous absorption of 1,1,2,2-... 

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