# Pharmacokinetics of Marine-Derived Drugs
## 3 Pharmacokinetics Studies in Animals
### Elimination
#### 3.4.3 Sea Cucumber-Derived Compounds  
The elimination of EA (**8**) and HA (**9**) isolated from _Pearsonothuria graeffei_ was very rapid after i/v injection in rats. The concentration of EA in plasma decreased approximately 10.5-fold in 15 min and remained stable (0.2 \(\upmu\)g/mL) two hours after injection. The elimination of HA was slower than EA. Its concentration decreased 10.5-fold in approximately one hour after injection and remained steady until two hours post-administration. The authors suggested that the difference in clearance was due to the specificity of oligoglycos' structures and the higher concentration of HA in the extract, whereas the final concentration of both compounds was nearly similar. The detection of EA and HA in the serum of rats within 24 h indicated its slow elimination after peroral administration [39]. The concentrations of both oligoglycosides EA and HA in the intestine of rats reached a maximum at 2 h after peroral administration of extract (300 mg/kg). Then, their concentrations decreased, followed by the second maximum at six hours. The authors associated this finding with the enterohepatic circulation and secretion of oligoglycosides with bile acid into the intestine. The concentration of metabolites decreased in the intestine 6 (metabolites of HA) and 4 h (metabolites of EA) after extract administration. Both oligoglycosides and all their six metabolites were found in urine. Notable, the concentration of EA was significantly higher than that of HA. Conversely, the metabolites of HA were more abundant than those of EA. This suggests that EA is more easily excreted in urine. The authors explained the absence of metabolites with the one sugar moiety in the feces by its relatively high absorption rate in the gut [142]. Both saponins EA (**8**) and HA1 (**9**) were detected in plasma 24 h after i/v injection in rats, whereas the T\({}_{1/2}\) of HA1 was half that T\({}_{1/2}\) of EA. The T\({}_{1/2}\) of EA after peroral administration was relatively shorter (\(\
eg\)23%) compared with i/v injection (Table 2). The bioavailability of EA was 59%. HA1 was not detected in the plasma after oral administration [38].  
The T\({}_{1/2}\) of fromoside A (**11**) after i/p injection was 1.6-fold longer compared with that after i/v injection. The body Cl was 6.35 mL/min/m\({}^{2}\) after i/v injection vs. 127 mL/min/m\({}^{2}\) after i/p injection. The calculated F was 20% after i/p administration of frondoside A [41].  
After peroral administration in mice, cumaside (**12**) was rapidly eliminated with the T\({}_{1/2}\) ranging from 0.3-1.4 h, and CL varied within 793-3519 \(\upmu\)g/min depending on the organ. The i/p administration was followed by significantly prolonged T\({}_{1/2}\) (9-22 h) and delayed Cl (18.7-94.3 \(\upmu\)g/min) depending on the organ [56; 105]. Cumaside was slowly eliminated from the spleen of mice after i/p administration with a Cl of 21.5 mL/min and T\({}_{1/2}\) of 91.6 min [47]. During pharmacokinetic studies, the absorption rate of cumaside and its distribution were the same after i/p and peroral administration in mice. It does not accumulate and is quickly eliminated from the organs after peroral administration. Based on these data, peroral administration was suggested as a rational method for future clinical trials [55; 104].