Effect of repeated skin administration on in vivo percutaneous absorption of drugs.
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Biomedical subjects
Publications and source records attributed to D A Bucks.
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The effects of daily repeated topical application and of washing on the percutaneous absorption of malathion have been investigated in guinea-pigs. Skin absorption was determined indirectly by measurement of radioactivity excreted into the urine following topical administration of 14C-labelled malathion, with correction of these values for incomplete renal elimination. Malathion was applied at a concentration of 5 mg/cm2 every 24 hr to the same site on the post-auricular bald area for 15 days. Doses 1, 8 and 15 were radiolabelled. The effect of multiple application and washing was assessed by Newman-Keuls multiple range test for statistical significance. The percutaneous absorption of malathion was 2-3 times higher with washing than without. There was no significant increase (P greater than 0.05) in the percutaneous absorption of malathion with repeated application without washing. These studies suggest that the total penetration of malathion resulting from daily topical dosing without daily washing may be predicted from a single-dose application to the same unwashed site at an equivalent surface concentration, and also that repeated washing with soap and water may significantly decrease the barrier function of guinea-pig skin.
This study determines the in vivo percutaneous absorption of paraquat in humans. Three skin sites of application were used in a crossover manner for six subjects. The percents of applied dose (9 micrograms/cm2) absorbed were 0.29 +/- 0.2 (SD) for the leg, 0.23 +/- 0.1 for the hand, and 0.29 +/- 0.1 for the forearm. This gives an in vivo absorption rate of 0.03 microgram/cm2 for the 24-h exposure. Paraquat can be absorbed in vivo through the skin of humans; however, it is considered a minimally absorbed chemical.
Prediction of exposure and toxic potential of pesticides such as malathion are routinely based upon acute exposure and single-dose percutaneous absorption determination. What has become obvious with pesticide exposure such as the malathion spraying for the medfly is that chronic daily exposure is the more relevant situation. Our objective was to determine the percutaneous absorption of chronically applied malathion in man and to compare chronic absorption to single-dose absorption. The experimental design was to first topically apply [14C]malathion to human male volunteers. This procedure was followed by repeated administration of nonradioactive malathion to the same site of application (ventral forearm). [14C]Malathion was reapplied (Day 8) when urinary excretion of radioactivity from the first application reached minimum detectable levels. The first [14C]malathion absorption was compared to the second [14C]malathion application. The percutaneous absorption from the first [14C]malathion application was 4.48 +/- 1.3% (SD) of the applied dose. The absorption from the second [14C]malathion administration was 3.53 +/- 1.0%, a value not significantly (p greater than 0.05) different from the first application. Therefore, for malathion the single-dose application data are relevant for predicting the toxic potential for longer-term exposure.
The effect of skin delipidization in humans on the percutaneous penetration of hydrocortisone was investigated in a cross-over trial. The delipidizing agent was 1:1:1 trichloroethane, a common industrial organic solvent. The findings do not show any significant difference in the topical absorption of hydrocortisone with and without skin delipidization. It was postulated that the natural skin barrier was reestablished by the metabolic cutaneous lipid regeneration concomitant with the absorption of the fatty ingredients from the cream.
Our objective was to determine the percutaneous absorption of hydrocortisone in psoriatic skin. [14C]-Hydrocortisone formulated as a 0.5% cream was applied to sharply defined erythematous plaques with silvery scales on the dorsal forearm of four hospitalized psoriatic patients. An average 2.32 +/- 1.4 (SD) percent of the applied dose was absorbed. The absorption of the same dose from the dorsal forearm of six normal subjects was 2.45 +/- 1.2%. We conclude that for presumably stable psoriatic plaques, the percutaneous absorption of hydrocortisone is the same as for normal skin.
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The objectives of this study were to determine the dermal absorption, systemic elimination, and dermal wash efficiency for polychlorinated biphenyls (PCBs). 14C-Labeled 42% PCB and 14C-labeled 54% PCB were topically and parenterally administered to rhesus monkeys and guinea pigs. Dermal absorption, determined by 14C urinary excretion, was extensive. In guinea pigs, 33% of the applied 14C-labeled 42% PCB dose and 56% of the 14C-labeled 54% PCB dose were absorbed. In rhesus monkeys, 15-34% of the labeled 42% PCB was dermally absorbed, depending on the magnitude of the applied dose. 14C-labeled 42% PCB applied to guinea pig skin was immediately washed with water and acetone. Only 59% of the applied dose was removed from the skin. A post-24-h washing removed only 1% of applied labeled 42% PCB and 20% of applied labeled 54% PCB. Postcontamination washing cannot be assumed to remove all contaminated PCB from skin. The body elimination of 14C was continuous and slow, with elimination half-lives on the order of 2-3 d in the guinea pig and 4-7 d in the monkey. Only 50-65% of an intramuscular dose could be accounted for in urine and feces for up to 28 d excretion. The elimination half-lives following topical administration were not much greater than that following intramuscular administration. This suggests that PCBs are rapidly and extensively absorbed through the skin, and that they are then probably generally distributed throughout the body, and then slowly eliminated.