Guinea pigs clearance

Hirom [71,72] demonstrated more than three decades ago that the route of excretion of xenobiotics is dependent upon MW by testing up to 75 compounds in rat, guinea-pigs, and rabbits. Lower MW compounds (< 350) were mainly eliminated in the urine (>90%). As MW increased from 350 to 450, a sharp increase in the fraction of compound eliminated in the bile occurred, and for MW > 450, compounds were eliminated 50-100% in the bile in all three species. Smith [73] correlated the log of free metabolic and renal clearance (ml/min/kg) with log D, and found a similar relationship. Metabolic clearance increases with increasing log D, while renal clearance decreases with increasing log D. 

Involvement of tissue esterases is documented for zomepirac glucuronide, which undergoes rapid hydrolysis in vivo in the guinea pig and rabbit [30], Co-administration of (phenylmethyl)sulfonyl fluoride (an inhibitor of esterases) dramatically decreased the apparent plasma clearance of zomepirac glucuronide, and, in other experiments, strongly increased the apparent plasma clearance of zomepirac administered as such. 

DiVincenzo GD, Kaplan CJ, Dedinas J. 1976. Characterization of the metabolites of methyl n-butyl ketone, methyl iso-butyl ketone, and methyl ethyl ketone in guinea pig serum and their clearance. Toxicol AppI Pharmacol 36 511-522. 

Several factors are involved in the wide variation in tumor inhibitory activity of asparaginases from different sources (98). One obvious possibility is the rate of clearance of the enzyme from the circulation of the host animal, and Broome (26) was the first to obtain evidence implicating half-life as a factor in antitumor effectiveness. Guinea pig serum asparaginase, for example, has a half-life time of 11-19 hr, while a partially purified yeast asparaginase preparation without antilymphoma activity is almost completely cleared within 30 min. Differences in half-life alone cannot explain the differences in antitumor activity in all cases, however and the question still remains as to what structural features are responsible for rapid or slow clearance. Mashburn and Landin (85) have suggested that differences in half-life time may be related to the isoelectric point of the enzyme, and evidence also exists to support the idea that the tumor inhibitory activity of some asparaginases is related to their K, values (59, 67). 

In experimental animals, administration of a diet containing 2.5 or 5% activated charcoal substantially reduced mortality due to a single lethal oral dose of 2,3,7,8-TCDD in rats, mice, and guinea pigs (Manara et al. 1984). Also, feed with 0.25 or 0.5% cholic acid had a similar protective action in mice (Manara et al. 1984). The effect of activated charcoal was attributed to increased clearance of unabsorbed... 

Wahlberg, J. E. Skin clearance of iontophoretically administered Chromium ( Cr) and Sodium ( Na) ions in the guinea pig. Acta Dermatovener (Stockholm) 50 255, 1970. 

Churg A, Wright JL, Gilks B, et al. 1989b. Rapid short-term clearance of chrysotile compared with amosite asbestos in the guinea pig. Am Rev Respir Dis 139 885-890. 

Jones PM, Robinson ICAF (1982) Differential clearance of neu-rophysin and neurohypophysial peptides from the cerebrospinal fluid in conscious guinea pigs. Neuroendocrinology 34 297—302. 

---