Intramuscular dose, excretion differences

Because these experiments illustrate the excretion differences between dermal. Intramuscular, and oral dose excretion, the excretion differences between compounds, and also problems about which urinary metabolite to monitor (see 44). a very comprehensive experimental design would be necessary to correctly model dermal exposure, absorption, and urinary metabolite levels. Statistical problems, centering around replicate variation and the resulting necessity for abnormally large numbers of replications, could drive the costs of such an experiment In small animals, and certainly in humans, to prohibitively high levels. 

The metabolism of danofloxacin does not differ in swine. When five daily intramuscular injections of 1.25 mg radiolabeled danofloxacin/kg bw were given to pigs, the parent drug accounted for 72-81 % of the radioactivity excreted in feces and urine over the 5- day dosing period (143). In feces, 5-7% of the radioactivity was identified as A-desmethyl danofloxacin. In urine, 2-3% was A-desmethyl danofloxacin, 10-14% danofloxacin-A-oxide, and 3% danofloxacin glucuronide. 

Following intramuscular administration to sheep of 1 mg xylazine/kg bw, two-thirds of the injected dose could be absorbed within 10 min (113). The drug was rapidly distributed to different tissues, and rapidly eliminated. The rapid elimination of xylazine in sheep is probably related to its intense metabolism rather than to its rapid renal excretion. This hypothesis was supported by the lack of significant amounts of the intact drug in urine samples collected every 10 min from treated sheep. 

Rates of bismuth excretion after intramuscular injection into rabbits were monitored for 13 different bismuth compounds, and water-soluble compounds were seen to be excreted more rapidly than those suspended or dissolved in oil. Excretion of bismuth during 4 days ranged from 82.2% of the dose for an aqueous solution of bismuth thioglycollate to 1.9% for an oil suspension of bismuth oleate, though excretion contin-... 

Chlordiazepoxide is well absorbed after oral administration, and peak blood concentration usually is reached in approximately 4 hours. Intramuscular absorption of chlordiazepoxide, however, is slower and erratic. The half-life of chlordiazepoxide Is variable but usually quite long (6-30 hours). The initial N-demethylation product, N-desmethylchloridiazepoxide, undergoes deamination to form the demoxepam (Fig. 22.18), which is extensively metabolized, and less than 1 % of a dose of chlordiazepoxide is excreted as demoxepam. Demoxepam can undergo four different metabolic fates. Removal of the N-oxide moiety yields the active metabolite, N-desmethyIdiazepam (desoxydemoxepam). This product is a metabolite of both chlordiazepoxide and diazepam and can be hydroxylated to yield oxazepam, another active metabolite that is rapidly glucuronidated... 

P) Rats, The rat differs from other species in the whole-body retention, excretion, and distribution of iAs and its metabolites. In an early study, CouLSON and associates (1935) reported that rats excreted As derived from ingestion of shrimp faster than iAs which was added to the diet. Hunter and coworkers (1942) noted that the erythrocyte was the major depot for As following administration of iAs. Subsequent studies have confirmed the high accumulation and retention of As in the rat erythrocyte. In a comparison among species 48 h after intramuscular administration of sodium p" As ] arsenate, Lanz and coworkers (1950) found that the blood compartment of the rat accounted for nearly 45% of the administered dose of " As. In contrast, the blood compartment in cat accounted for 5.6% of the administered dose in dog, 0.1% in rabbit, 0.27%, in guinea pig, 0.25% in chicken, 0.19% and in mouse, 0.07%. 

---