# Pharmacokinetics of Marine-Derived Drugs
## 4 Pharmacokinetics Studies in Humans
It was long believed that fucoidan, due to its high molecular weight and the absence of digesting enzymes in humans, cannot penetrate the blood after peroral administration [167]. [PERSON] et al. detected fucoidan in human blood for the first time after peroral administration. The group of 40 volunteers was administered 3 g of 75% sulfated galactofuran with an MW of 713 kDa isolated from _Undaria pinnuaffida_ three times a day for 12 days. The median concentration of fucoidan in the plasma was 12.989 mg/L, and the oral bioavailability was calculated as less than 0.6% [31]. In another experiment, 10 healthy male subjects were administered 1 g of fucoidan from _Cladosiphon okamuraus_. Fucoidan was found in serum and urine 3 h after administration. During 9 h of observation, the time-dependent elevations of fucoidan concentration in the serum (up to 100 ng/mL) and urine (up to 1000 ng/mL) were registered. No difference in fucoidan concentration in the serum and plasma was detected. The MW (66 kDa) of the ingested fucoidan in the serum remained unchanged, whereas the MW (1.8-3.1 kDa) of fucoidan in urine was significantly lower, which evidenced the polysaccharide metabolism [49]. Later, a group of 48 volunteers was involved in new experiments. Both male and female subjects were administered 100 g of 100 g of Okinawa mozuku from _Cladosiphon okamuraus_ containing 1 g of fucoidan. The highest fucoidan content (37.2 ng/mL in men and 14 ng/mL in women) was observed in urine 9 h after administration [168]. A large study on 396 volunteers was performed with mozuku fucoidan isolated from _Nemacystus decipients_ seaweed. Subjects drank a beverage with 3 g fucoidan [169]. Fucoidan was observed in the urine of 295 subjects. The concentration of fucoidan in urine (as evidenced by ELISA) ranged between 332.3 \(\pm\) 357.6 and 240.1 \(\pm\) 302.4 ug/g Cr. Higher concentrations were observed in subjects who consumed more seaweed in their daily diet. The authors confirmed that fucoidan is absorbed after peroral administration in humans and excreted with urine. Unfortunately, the authors did not provide details about fucoidan's molecular weight, sulfate content, or monosaccharides composition. To understand the effect of _Helicobacter pylori_ on fucoidan absorption, the group of 259 subjects consumed 3 g mozuku fucoidan in a health drink [170]. Fucoidan was analyzed in urine. Suppressed absorption of fucoidan was observed in _H. pylori_-positive volunteers aged \(\geq\) 40 years who consumed mozuku once monthly. However, there was no association in the group of _H. pylori_-negative subjects irrespective of the frequency of mozuku consumption and age. Notably, the basal fucoidan level in urine was significantly higher in the _H. pylori_-positive group. This evidenced the contribution of _H. pylori_ to fucoidan metabolism. Taken together, these results showed that fucoidan is absorbed after peroral administration and metabolized in the human excretory system. However, its concentration in blood and urine was relatively low [171]. This is in agreement with in vivo data that evidenced the rapid absorption and slow elimination of fucoidan after peroral administration [27; 28; 35]. We have not found publications that reported the other pharmacokinetic parameters of fucoidan, such as AUC, Cl, T\({}_{1/2}\), etc., in humans. Such studies are essential for better understanding the mechanisms of fucoidan efficacy. The bioavailability and pharmacokinetics of the synthetically derived astaxanthin _E_/Z-isomer were demonstrated in three healthy male volunteers. Subjects were treated with water-dispersible astaxanthin containing beadlets at a single dose of 100 mg. Astaxanthin was found in plasma, and no metabolites were detected by HPLC. The C\({}_{\text{max}}\) of 1.3 mg/L was observed at 6.7 \(\pm\) 1.2 h. The AUC was 42 \(\pm\) 3 mg:h/L. The blood circulation was prolonged. T\({}_{1/2}\) varied between 11.4 and 32.1 h depending on the subject. About 12% of the maximal concentration of astaxanthin was detected in plasma 72 h after administration.