# Pharmacokinetics of Marine-Derived Drugs
## 3 Pharmacokinetics Studies in Animals
### Absorption
#### 3.1.3 Sea Cucumber-Derived Compounds  
Sea cucumbers are echinoderms belonging to the Holothuriidae. These organisms have been used as functional food [4] and a source of bioactive compounds [94]. The extract, containing lanostane-type triterpene oligoglycosides echinoside A (**8**) (EA) and holothurin A (**9**) (HA), was isolated from sea cucumber _Pearsonothuria graeffei_. Among others, EA and HA show promising anticancer activity [95; 96]. The pharmacokinetic was characterized after single i/v (0.2 mg/kg) and peroral (30 mg/kg) administration of extract to rats. Both saponins were rapidly absorbed and appeared in serum at 4.0 (EA) and 0.94 ug/mL (HA) in the first minute after i/v injection. The serum concentration-time functions for EA and HA are characterized with two maxima after peroral administration. The concentrations of EA and HA at 0.5 h reached 0.11 and 0.2 ug/mL, respectively. The first C\({}_{\text{max}}\) was 0.83 ug/mL (EA) and 0.34 ug/mL (HA) at a T\({}_{\text{max}}\) of 3 h and the second C\({}_{\text{max}}\) were 0.24 ug/mL (T\({}_{\text{max}}\) = 7 h) for EA and 0.27 ug/mL (T\({}_{\text{max}}\) = 9 h) for HA [39].  
[PERSON] et al. investigated echinoside A (EA) (**8**) and holotoxin A1 (HA1) (**10**), isolated from _Apostichopus japonicus_[38]. The cytotoxic and radioprotective effects have been described, among others, for HA1 [97; 98]. EA and HA1 (20 mg/kg) were i/v and perorally administered to rats. Both saponins were quickly detected in plasma after i/v injection with C\({}_{\text{max}}\) of 4.0 and 2.87 ug/mL for EA and HA1, respectively. However, the AUC value for EA was 2.5-fold higher than for HA1. After oral administration, EA was detected in rat plasma 1 h, followed by an increase up to 3 h (Table 2). This is evidence of its gradual absorption into plasma. In contrast, HA1 was not detected in plasma after peroral administration. In vitro, EA penetrates across the Caco-2 cell monolayer by passive diffusion without assistance by P-glycoprotein, whereas the transport of HA1 through the monolayer was poor. This agrees with in vivo data [38].  
The frondosides A, B, and C represent a group of triterpen glycosides isolated from Atlantic sea cucumber _Cucumaria frondosa_. Frondosides are known as potent anticancer compounds against the adenocarcinomas of different organs, as well as leukemia [99; 100; 101]. The pharmacokinetics of the most active frondoside, frondoside A (**11**) (100 ug/kg), was studied in mice following i/v and i/p injections. The C\({}_{\text{max}}\) of frondoside A in plasma after i/v injection was approximately seven-fold higher than after i/p injection, whereas the AUC after i/v injection was 4.8-fold higher than after i/p injection (Table 2). After i/v injection, the plasma concentration-time function was two-exponential with t\({}_{\text{1/2 $\alpha$}}\) of 2 min and t\({}_{\text{1/2 $\beta$}}\) of 158 min. However, frondoside A was not stably detected in the plasma after peroral administration (100 and 500 ug/kg) in rats due to the sensitivity of the method (Table 1) [41].  
A triterpene glycoside cucumarioside A\({}_{2}\)-2 (**12**) (cumaside), isolated from Far Eastern sea cucumber _Cucumaria japonica_, shows anticancer and immunostimulatory activities [100; 102; 103]. The pharmacokinetics of cumaside was studied after i/p and peroral administration in mice (5 mg/kg). Cumaside was quickly absorbed in blood after i/p administration (C\({}_{\text{max}}\) = 114 ug/mL, T\({}_{\text{max}}\) = 4 min). The absorption after peroral administration was rather slow (C\({}_{\text{max}}\) = 75 ug/mL, T\({}_{\text{max}}\) = 40 min) [104]. In contrast, Aminin reported a similar absorption of cumaside after i/p and peroral administration with relatively the same T\({}_{\text{max}}\), C\({}_{\text{max}}\), and AUC (Table 2) [55].