# Pharmacokinetics of Marine-Derived Drugs
## 3 Pharmacokinetics Studies in Animals
### Distribution  
#### 3.2.1 Algal-Derived Compounds  
The distribution of ficoidan (**1**) was reported after i/v, peroral, and transdermal applications. Equal values of MRT of \(5.48\pm 1.78\) h and \(5.30\pm 1.65\) h were observed for ficoidan with an MW of 100 kDa after i/v injection and peroral administration, respectively [35]. The high-MW ficoidan, after peroral administration to rats, showed prolonged MRT in blood (6.79 h) and accumulation in organs with a filtering function, such as spleen, kidneys, and liver (Table 3) with MRT of 14.57, 12.39, and 9.26 h, respectively [27]. Similar results were observed after i/v injection of FITC-labeled commercially available ficoidan in mice. Fucoidan quickly distributed to the liver and kidney and reached the maximal concentration at a T\({}_{\text{max}}\) of 0.5 h. The MRT values in blood, liver, spleen, lung, and kidney were 3.23, 14.66, 303.96, 6.88, and 20.14 h, respectively [32]. The maximal accumulation was observed in the kidney. However, it was not detected in the brain or the heart (Table 3) [32]. These data support the renorprotective effects of ficoidan that were reported previously [61,136]. After topical application in rats, a high concentration of ficoidan was observed in skin in 15 min, which started to decrease in 1 h. This indicates that, initially, the epidermis was saturated with the drug. However, after one hour, the concentration of ficoidan increased in muscles and plasma with muscle-plasma concentration ratios of 1.77 and 1.75 at the first and second hours postdose, respectively. The linear pharmacokinetics was observed at the doses of 50-150 mg/kg [28]. The mean V\({}_{\text{ss}}\) for GRFT after i/v injection was 0.5 L, without statistically significant dose dependence. After s/c injection, V\({}_{\text{ss}}\) decreased from 1.2 to 0.2 L at 10 and 20 mg/kg, respectively [51]. The maximal amount of GRFT was observed in the spleen, followed by the kidney and liver of mice after multiple-dose s/c injection. Due to intensive accumulation of GRFT in spleen, the authors advised to control the immune response elicited by GRFT treatment to prevent GRFT immune-related toxicity [68]. After i/p and s/c injection in mice, sodium ablates were found in the spleen, liver, and kidneys [73]. After i/v injection (139 mg/kg) in mice, halomon (**3**) was quickly absorbed and distributed to tissues. At 5 min after injection, the maximal concentration of halomon was detected in the heart, followed by lungs, kidney, brain, liver, spleen, skeletal muscles, and fat. Notably, halomon crossed the blood-brain barrier. Its concentration in the brain was comparable with concomitant concentrations in plasma and other tissues. The lipophilic nature of halomon and multiple halogens in the structure could explain its remarkable persistence in fat tissue. This quick and wide distribution may explain the rapid reactivity of halomon to cancer cells in vitro [33]. The tissue distribution of fucoxanthin (**6**) and its metabolites (fucoxanthin (**23**) and amarouciaxanthin A (**24**)) was studied in mice after peroral administration of fucoxanthin. The maximal concentration of both metabolites was detected in the liver, followed by lung, kidney, heart, and spleen. Interestingly, this order in tissue distribution was the same for both metabolites. Fucoxanthin was also detected in all the above-mentioned tissues. High concentrations were found in the heart and liver. In adipose tissue, amarouciaxanthin A was more abundant. Fucoxanthinol and amarouciaxanthin A were present in adipose tissue until 72 h after the administration of fucoxanthin. However, in other tissues, these metabolites were not detectable after 24 h [80]. The mean distribution volume of fucoxanthin after i/v injection in rats was much lower than the V\({}_{\rm ss}\) of its metabolite fucoxanthin (0.7 L/kg vs. 8.8 L/kg). After peroral administration, the difference in V\({}_{\rm ss}\) for compounds was not statistically significant [42].