# Pharmacokinetics of Marine-Derived Drugs
## 3 Pharmacokinetics Studies in Animals
### Elimination  
#### 3.4.1 Algal-Derived Compounds  
The Cl of ticoudan (**1**) with an MW of 100 kDa was 0.0037 mg/ug/mL/h after i/v injection and 0.138 mg/ug/mL/h after peroral administration in rats [35]. The Cl of FITC-labeled commercially available fucoidan was 0.25 mg/(ug/g)/h after i/v injection in mice [32]. Low-MW fucoidan was not detected in serum 6 h after i/v injection in rabbits [36]. The concentrations of low- and medium-MW fucoidans from _L. japonica_ in urine 48 h after peroral administration in rats (800 mg/kg) were 1206.0 and 874.4 ug, respectively [34]. The authors suggested that due to the rapid penetration and retention in the skin, fucoidan showed prolonged T\({}_{1/2}\) (20.75 \(\pm\) 9.43 h) in plasma and low bioavailability (F = 17.7% \(\pm\) 7.7%) after topical application in rats [28]. Fucoidan with an MW of 100 kDa was characterized by equal T\({}_{1/2}\) (4.01 and 4.1 h, respectively) after i/v injection and peroral administration in rats. The bioavailability was 8.91% [35]. The FITC-labeled commercially available fucoidan was not detected in blood 4 h after i/v injection in mice [32]. The difference in T\({}_{1/2}\) after i/v and s/c injections of GRFT at 10 mg/kg was statistically not significant, whereas an increase in dose up to 20 mg/kg led to a delay in elimination by approximately 2.6-fold after s/c injection when compared with i/v injection. GRFT was still detectable in the serum of rats after both i/v and s/c injection (10 mg/kg) up to 96 h. The bioavailability of GRFT after s/c injection was dose dependent (F = 43% at 10 mg/kg and 90% at 20 mg/kg). GRFT was found in feces and urine of rats within 24 h following i/v and s/c injections. The concentration of GRFT in urine after peroral administration was below the detection limit, but it was found in feces. GRFT was not orally bioavailable even after multiple doses of treatment. However, after multiple doses of peroral administration, GRFT was found in feces and urine [51]. About 51 ng/mL of GRFT was found in the plasma of mice after s/c injection (50 mg/kg) at 24 h posttreatment. GRFT was still detectable through day 14 after treatment [68]. After i/p injection of sodium alginate in mice, the T\({}_{1/2}\) was 12.5 h. The bioavailability of sodium alginate were 44% and 5% following i/p and s/c injections, respectively. Alignates were excreted with urine [73]. Alginate oligosaccharides after peroral administration in mice was eliminated with urine with a C\({}_{\text{max}}\) of 425 ug/mL at 30 min, followed by a rapid decrease. After 6 h, AOs was still detectible in urine [43]. In another study, eight fractions of sodium alginate oligosaccharides were obtained by lyase enzyme degradation. The P8 fraction was administered to rats at 3 g/kg. At 24 h after administration, about 60% of P8 was excreted in the feces and 5% in the urine [154]. About 73-79% of alginic acid and its salts were excreted by rats in feces 72 h following peroral administration (90.4 mg/kg) [155]. About 86-91% of sodium alginate labeled with 14C was excreted in rat feces after 17 h of feeding a diet containing about 10% alginate. About 0.1-0.2% of alginate was eliminated with urine, whereas only 0.002-0.007% was found in plasma [156]. Halomon (**3**) was eliminated with a Cl of 36-56 mL/min kg after i/v injection. The clearance was non-linearly dose dependent at doses of 20-135 mg/kg. Halomon bioavailability was 45%, 47%, and 4% after i/p, s/c, and peroral administration, respectively [33]. The urinary excretion of halomon was minimal (0.0034-0.0046%). Its hepatic concentration decreased rapidly and was relatively low compared with other tissues and plasma. Therefore, the authors suggested biliary excretion or hepatic metabolism as the major routes of halomon elimination [33]. The elimination of fucocamthinol (**23**) (T\({}_{1/2}\) = 4.5 h) was faster than amarouciaxanthin A (**24**) (T\({}_{1/2}\) = 6.7 h) after peroral administration of fucoxanthin (**6**) in mice. Both metabolites were relatively quickly eliminated from the liver (T\({}_{1/2}\) = 2.5 h).