ABSTRACT
The pharmacokinetics and hepatic metabolism of [3H] ivermectin (IVM) and [3H]cyclosporin A (CSA) were investigated in a subpopulation of the CF-1 mouse stock naturally deficient in mdr1a p-glycoprotein (PGP). A survey of key drug-metabolizing activities in liver fractions from PGP-deficient (-/-) or wild-type (+/+) animals indicated the two subpopulations are not different in hepatic metabolic activity and capacity. Intravenous pharmacokinetics of CSA were identical between the two groups, and results from microsomal incubations indicated similar biotransformation of IVM and CSA in liver. Intestinal excretion of [3H]IVM and [3H]CSA was enhanced in PGP (+/+) animals. Absence of PGP resulted in higher blood concentrations of IVM after oral dosing, suggesting enhanced absorption of IVM in (-/-) mice. Concentrations of [3H]IVM and [3H]CSA were always greater in the brains of (-/-) mice compared with (+/+) mice after either i.v. or oral administration. In contrast, liver concentrations of either compound were not different between (+/+) and (-/-) animals after an i.v. dose. These results show the PGP (-/-) and (+/+) subpopulations of CF-1 mice are useful for studying the role of mdr1a PGP in systemic exposure and tissue disposition of PGP substrates in the absence of metabolism differences.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B/deficiency , Cyclosporine/pharmacokinetics , Ivermectin/pharmacokinetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Animals , Bile/metabolism , Biotransformation , Brain/metabolism , Cyclosporine/blood , Intestinal Mucosa/metabolism , Ivermectin/blood , Liver/metabolism , Male , Mice , Mice, Knockout , Tissue DistributionABSTRACT
The effect of various hand washing regimens on transfer of bacterial contaminants from the hands to a hydrogel contact lenses was evaluated. Each of 47 subjects performed 5 different hand washing procedures, and then handled a new, sterile hydrogel contact lens. The lenses were cultured to determine colony-forming units (CFUs) and microbial identity. Median CFUs on lenses handled after washing with water, soap and water, or soap and water followed by towel drying were higher than the median CFU for lenses handled after no hand washing. The median CFU for lenses handled after soap and water washing followed by an alcohol wipe was not different from the no washing group. The majority of the contaminants were identified as Staphylococcus epidermidis. These results show that ordinary hand washing alone does not decrease, and may even increase, the amount of contaminants transferred from the hands to a hydrogel lens. Use of an alcoholic wipe after hand washing reverses this effect. Hand washing is still recommended in contact lens hygiene for removal of more pathogenic contaminants.
