indication

For the treatment of patients infested with Sarcoptes scabiei or pediculosis capitis who have either failed to respond to adequate doses, or are intolerant of other approved therapies.

pharmacology

Scabies is a common, highly pruritic infestation of the skin caused by Sarcoptes scabiei (lice). It is a very contagious condition with specific lesions, such as burrows, and nonspecific lesions, such as papules, vesicles and excoriations. The typical areas of the body it affects are finger webs, scalp (hair), wrists, axillary folds, abdomen, buttocks, inframammary folds and genitalia (males). It is characterized by intense night-time itching. Scabies is spread through close personal contact (relatives, sexual partners, schoolchildren, chronically ill patients and crowded communities). Scabies infestations and the corresponding symptoms can be eliminated by killing the scabies with topical insecticides or scabicides. Lindane is a scabicide that is essentially an organochloride insecticide.

mechanism of action

Lindane is an organochloride insecticide that has similar neurotoxic protperties to DDT. It exerts its parasiticidal action by being directly absorbed through the parasite's exoskeleton (primarily lice, or scabies) and their ova. The gamma-aminobutyric acid (GABA(1)) receptor/chloride ionophore complex is the primary site of action for lindane, and other insecticides such as endosulfan, and fipronil. Blockage of the GABA-gated chloride channel reduces neuronal inhibition, which leads to hyperexcitation of the central nervous system. This results in paralysis, convulsions, and death. Lindane has very low ovicidal activity.

toxicity

Lindane is a moderately toxic compound via oral exposure, with a reported oral LD₅₀ of 88 to 190 mg/kg in rats. Gamma-HCH (which constitutes 99% of lindane) is generally considered to be the most acutely toxic of the isomers following single administration. It is moderately toxic via the dermal route as well, with reported dermal LD₅₀ values of 500 to 1000 mg/kg in rats, 300 mg/kg in mice, 400 mg/kg in guinea pigs, and 300 mg/kg in rabbits. Acute exposure to lindane may lead to central nervous system stimulation (usually developing within 1 hour), mental/motor impairment, excitation, clonic (intermittent) and tonic (continuous) convulsion. Other adverse reactions include central nervous system toxicity, as well as skin and gastrointestinal changes.

biotransformation

Primarily hepatic through dechlorination leading to 2-chlorophenol, 0-chlorophenol, chlorocyclohexane, chlorocyclohexanol.

absorption

Lindane is absorbed significantly through the skin. A mean peak blood concentration of 28 nanograms per mL occurred in infants and children 6 hours after total body application of lindane lotion for scabies.

half life

18 hours