# Pharmacokinetics of Marine-Derived Drugs
## 3 Pharmacokinetics Studies in Animals
### Absorption
#### 3.1.1 Algal-Derived Compounds
The mean absorption t\({}_{1/2\alpha}\) was 1.45 h and mean distribution t\({}_{1/2\beta}\) was 2.45 h, without statistically significant dose dependence. The C\({}_{\text{max}}\) after s/c injection was 12-fold lower compared with i/v injection and was dose dependent. The difference in AUC was 2.4-fold only at 10 mg/kg and was statistically not significant at 20 mg/kg (Table 2). GRFT was not detected in serum in the 96 h after a single dose (20 mg/kg) of peroral administration [51]. The C\({}_{\text{max}}\) level of GRFT was 0.32 and 0.46 ug/mL in plasma of mice and guinea pigs, respectively, observed by day 11 after 14 days' consecutive s/c injection (10 mg/kg) [68]. Figure 1: Structures of marine-derived compounds: fucoidan (**1**); alginic acid (**2**); halomon (**3**); eckol (**4**); fucoxanthin (**5**); astaxanthin (**6**); chitosan (**7**); echinoside A (**8**); holduurin A (**9**); holdoxin A (**10**); fromodside A (**11**); cucumarioside A\({}_{2}\)-2 (**12**); 6-epi-ophiobolin G (**13**); dindolinonepyrane (**14**); ilimaquinone (**15**); marzamine A (**16**); echinochrome A (**17**); apidine (**18**); kahalalide F (**19**); dolastatin 10 (**20**); dolastatin 15 (**21**); bryostatin 1 (**22**); fucoxanthinol (**23**); amarouciaxanthin A (**24**); cetinexcidin 743 (**25**). Alginates (**2**) represent a group of copolymers of mannuronic and guluronic acids. These anionic polysaccharides are isolated predominantly from brown algae. Due to their high ability for gel formation and their specific viscosity-related properties, alignates have been extensively used in pharmaceutical formulations as hydrophilic drug carriers, for coating, film formation, and as matrix materials for targeted drug delivery [70; 71; 72]. Two sodium alignates (MW = 200 kDa) with uluronic acid contents of about 44% and \(<5\%\) were not absorbed following peroral administration to mice. After i/v injection, the plasma concentration-time function was two-exponential with t\({}_{1/2\alpha}\) of 4 h min and t\({}_{1/2\beta}\) of 22 h. After i/p injection, the C\({}_{\text{max}}\) in plasma was observed at 5-6 h [73]. Alginate oligosaccharidescharide (AOs), containing the dimer, trimer, and tetramer of commercial sodium alginate, was obtained by lyase enzyme degradation. In contrast to the data reported by [PERSON] et al., [73] AOs was detected in the plasma of mice after peroral administration (10 mg per mice) with C\({}_{\text{max}}\) of 24.5 \(\mu\)g/mL (about 0.49% of administered dose) at T\({}_{\text{max}}\) of 5 min, followed by a rapid decrease. After 2 h, AOs was below the detection limit [43]. Halomon (**3**), a halogenated monoterpene 6(_R_)-bromo-3(_S_)-(bromomethyl)-7-methyl-2,3,7-trichloro-1-octene, was isolated from the red alga _Portieria hornemannii_. It demonstrates potent activity against cancer cells [74; 75]. Pharmacokinetics of halomon was studied in mice after i/v (20-135 mg/kg), i/p, s/c, and peroral (135 mg/kg) administrations. The concentration of halomon in plasma at 5 min after j/v injection was 85-100 \(\mu\)g/mL for female and 65-67 \(\mu\)g/mL for male mice. The pharmacokinetics of halomon in plasma was described by a two-compartment open linear model and was linear at all doses (20-135 mg/kg), as evidenced by the peak concentration and AUC. The bioavailability after s/c injection was 45%; after peroral administration, it was 4% [33]. Eckol (**4**) belongs to phlorotannins, which are derivatives of dibenzo-1_A_-dioxins. It contains phloroglucinol components linked to each other. Red and brown algae, in particular _Ecklonia stolonifera_, are known to produce eckol. Its therapeutic potential includes, but is not limited to, anti-bacterial anti-cancer, ant-coagulant, anti-diabetic, anti-hypertensive, and neuroprotective, radioprotective activities [76]. The pharmacokinetics of eckol was analyzed in silico using PreADMET software. Eckol was considered the lipophilic compound with logPo/w = 2.99. The human intestinal absorption was calculated as moderate (55.60%), and the plasma protein binding of eckol was 100%.