# Pharmacokinetics of Marine-Derived Drugs
## 3 Pharmacokinetics Studies in Animals
### Absorption
#### 3.1.6 Marine Compounds Derived from Other Species  
Aplidine (**18**) (syn. dehydrodidemnin B, plitidepsin) is a cyclodepispeptide with potent anticancer activity isolated from Mediterranean tunicate _Aplidium albicans_[127]. The absorption of aplidine was studied in rats. Two minutes after i/v injection at the dose of 700 \(\mu\)g/kg, the concentration of aplidine in blood was 100 ng/mL [44].  
Kahalalide F (**19**) is a cyclic depsipeptide found in Hawaiian mollusk _Elysia rufescens_ and the green algae _Bryopsis_ sp. [128]. This compound has considerable potential as an anticancer drug [129; 130]. The pharmacokinetic of kahalalide F was studied in mice. After an i/v injection of 278 \(\mu\)g/kg, the initial plasma concentration of kahalalide F was 1.55 \(\mu\)M. The plasma concentration-time function was two-exponential with t\({}_{1/2~{}\alpha}\) of 15.8 min and t\({}_{1/2~{}\beta}\) of 4.4 h [57].  
Dolastatins 10 (**20**) and 15 (**21**) are small peptides, isolated from the shell-less mollusks sea hare _Dolabella auricularia_, that have shown anticancer activities [131]. The pharmacokinetics of radio-labeleddolastatin 10 was studied in mice after i/v (0.24 mg/kg), s/c (0.32 mg/kg), and i/p administrations. A rapid decrease in dolastatin in plasma was observed after i/v injection. The dolastatin concentration in plasma after s/c injection increased slowly up to a C\({}_{\text{max}}\) of 11 ng/mL. The human, dog, and mouse plasma protein-binding for dolastatin was calculated as more than 81% [58]. After i/v injection in mice (1 mg/kg), both dolastatins (10 and 15) were detected in plasma at 5 min post-injection. The plasma concentration-time function was two-exponential with t\({}_{\text{1/2 $\alpha$}}\) of 0.04 h and 0.09 h and t\({}_{\text{1/2 $\beta$}}\) of 1.6 h and 0.52 h for dolostatins 10 and 15, respectively. The AUC dolastatin 10 was 1.6-fold higher than for dolastatin 15. The plasma binding of dolastatin 10 was more than 90% [59].  
Bryostatin 1 (**22**) is a cyclic macrolide isolated from a marine bryozoan, _Bugula meritina_[132]. It is known as an anticancer compound, a modulator of protein kinase C, and is used as a neurodegenerative agent [133,134]. In a pharmacokinetics study, bryostatin 1 was i/v- and i/p-injected in mice at the dose of 40 ug/kg. Following i/v injection, bryostatin 1 appeared in plasma at C\({}_{\text{max}}\) of 92.9 ng/mL. The plasma concentration-time function was two-exponential with t\({}_{\text{1/2 $\alpha$}}\) of 1.05 h and t\({}_{\text{1/2 $\beta$}}\) of 1.6 h and 22.97 h. After i/p injection, C\({}_{\text{max}}\) was 13.5 ng/mL. Although the C\({}_{\text{max}}\) after i/p injection was lower than after i/v injection, the AUC after i/p injection was 1.6-fold higher than after i/v injection (Table 2). These data provide evidence of good absorption and retention in blood after i/p injection [63]. In another study, the pharmacokinetics of bryostatin 1 was evaluated after i/v injection in mice at doses of 3.50 and 5.25 ug/kg. The peak concentration in plasma increased with increasing dose. The C\({}_{\text{max}}\) value was about 2.26 ng/mL at a high dose [135].