Percutaneous absorption and excretion of xenobiotics after topical and intravenous administration to pigs.
Interspecies comparisons suggest that the weaning pig is a suitable surrogate for man in percutaneous absorption studies. Despite known anatomical and physiological similarities between porcine and human skin, very few investigations of percutaneous absorption phenomena have been conducted in pigs. This study examined radiolabel excretion patterns after intravenous (iv) and topical administration of six 14C-radiolabeled compounds in weanling Yorkshire sows. Radiolabel recovery from excrement collected over 6 days following iv doses in physiological saline (200 micrograms, 10 muCi) showed that malathion (M), parathion (P), caffeine (C), and benzoic acid (B) were primarily excreted into urine (greater than 80%), while greater fractions of testosterone (T, 72%) and progesterone (R, 35%) were fecally eliminated. Percutaneous absorption was determined from total urine and fecal excretion of radiolabel after topical application, corrected for incomplete excretion following iv administration. Topical doses in ethanol (200 micrograms, 10 muCi) were applied at a surface concentration of 40 micrograms cm-2 and penetrated in the following rank order (percentage dose): B (25.7%) greater than R (16.2%) greater than C (11.8%) greater than T (8.8%) greater than P (6.7%) greater than M (5.2%). Fecal clearances of radiolabel, expressed as a percentage of total excretion, were greater after topical administration for four of the six compounds (B, C, P, and T, p less than 0.05). Calculations based on urinary excretion alone underestimated percutaneous absorption determined from total excretion by 5-30%, although the difference between the two estimates was statistically significant only for C (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Carver
M P
MP
Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Riviere
J E
JE
D000287:Administration, Topical; D000818:Animals; D005243:Feces / Q000032:analysis; D005260:Female; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D012869:Skin Absorption; D013552:Swine; D015262:Xenobiotics / Q000008:administration & dosage / Q000493:pharmacokinetics*
D015262:Xenobiotics