# Pharmacokinetics of Marine-Derived Drugs
## 3 Pharmacokinetics Studies in Animals
### Absorption
#### 3.1.4 Sea Fungus-Derived Compounds  
Marine fungi are a significant part of ocean biodiversity and have tremendous potential as a source of new drug candidates [105; 106]. Sesterterpene 6-epi-ophiobolin G (**13**) (MHO7), produced by a mangrove fungus _Aspergillus ustus_, exhibited promising anticancer activity in 41 cell lines [107]. MHO7 was detected in plasma at 0.5 h after peroral administration in mice (500 mg/kg). The first peak concentration was achieved at 8 h (Table 2), followed by a gradual decrease up to 15 h. The second peak was observed at 10 h. This indicated a possible secondary absorption of sesquiterpene [45]. Diindolinonepyrane (**14**), 2,5-bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-tertahydro-6H-pyran[a]isoindol-2-yl]-pentanoic acid (2,5-BHPA) isolated from marine fungi _Stachybortys longispora_, possesses significant thrombol activity [108; 109]. The linear pharmacokinetics was observed for 2,5-BHPA after i/v injection in rats at doses of 10-20 mg/kg. The concentration of 2,5-BHPA rapidly decreased in the blood after injection. The AUC was proportional to dose (412.2 and 899.1 ug/mL-min for 10 and 20 mg/kg, respectively) [37]. In another study, dogs were i/v-injected with 2,5-BHPA at doses of 2.5, 5.0, and 7.5 mg/kg. The AUC value increased linearly with increasing dose [40]. The shape of plasma concentration-time curves was the same as described previously for rats [37]. Low permeability and low recovery were observed for 2,5-BHPA in the Caco-2 model. The authors suggested that peroral administration is less appropriate than i/v injection [40].3.1.5. Marine Sponge-Derived Compounds. Marine sponges (phylum _Porifera_) are the most basal type of multicellular marine organisms. About 8000 species of sponges have been described. They significantly contribute as unique, renewable, and rich suppliers of new and valuable drug candidates [110]. Sponges produce different classes of compounds that display anti-bacterial, anti-fungal, antiviral, anti-spasmodic, cytotoxic, and other bioactivities [23; 111; 112; 113]. A sesquiterpene quinone ilimaquinone (**15**) (IQ), isolated from sponge _Hippiospongia metachromia_, exhibits anti-bacterial, antiviral, and anti-cancer activities [114; 115; 116]. Recently, the pharmacokinetics of IQ was reported in rats after peroral (10 mg/kg) administration. The C\({}_{\text{max}}\) of 943 ng/mL was observed at 2.5 h post-administration [117]. Later, the same group of authors investigated the pharmacokinetics of the mixture of IQ and epi-IQ after i/v (3 mg/kg containing 2 mg/kg of IQ and 1 mg/kg of epi-IQ) and peroral (30 mg/kg containing 20 mg/kg of IQ and 10 mg/kg of epi-IQ) administration in rats. The AUC for IQ was approximately six-fold higher than that of epi-IQ after i/v injection. After peroral administration, C\({}_{\text{max}}\) for IQ was 11.6-fold higher compared with epi-IQ, whereas the T\({}_{\text{max}}\) for both substances was almost the same (Table 2) [46]. The absorption of ilimaquinone after the peroral administration of the mixture seems to be faster compared with single-compound administration [117]. However, this difference was not statistically significant. \(\beta\)-carboline alkaloid manzamine A (**16**), isolated from a sponge of _Haliclona_ sp., exhibited potent antibacterial, anti-cancer, anti-malarial, and anti-HIV activities [56; 118; 119; 120]. In a pharmacokinetics study, manzamine A isolated from a sponge of the _Acanthostrongylophora_ genus was administered to rats by i/v (10 mg/kg) and peroral (50 mg/kg) routes. After i/v injection, the plasma concentration of manzamine A was about 40 \(\mu\)g/mL. The plasma concentration-time function was exponential. After peroral administration, manzamine gradually increased in plasma and reached C\({}_{\text{max}}\) of 1066 ng/mL at a T\({}_{\text{max}}\) of 10 h. Manzamine A has good solubility in acids. This is helpful for its absorption in the stomach.