Abstract
6-Methylcoumarin (6MC) is a semisynthetic coumarin with important in vitro and in vivo anti-inflammatory activity. In order to continue the pre-clinical characterization of this molecule, in vitro intestinal permeability, plasma profile and tissue distribution after oral administration in rats were studied. The permeability of 6MC was evaluated by the Caco-2 cellular model in both the apical-basal (A-B) and basal-apical (B-A) directions. The pharmacokinetics and biodistribution were evaluated in rats after oral and intraperitoneal administration at doses of 200 mg/kg. Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. This finding suggested that 6MC could be transported across the gut wall by passive diffusion. The plasma concentration-time curve showed that the maximum concentration (Cmax) was 17.13 ± 2.90 µg/mL at maximum time (Tmax) of 30 min for the oral route and Cmax 26.18 ± 2.47 µg/mL at 6.0 min for the intraperitoneal administration, with elimination constant of (Ke ) 0.0070 min-1 and a short life half time of (T1/2 ) lower that 120 min. The distribution study showed that 6MC has high accumulation in the liver, and widespread distribution in all the organs evaluated.
Highlights
The oral route is the most common route for administration of new drugs, as it is considered the safest and most convenient
According to the Biopharmaceutics Classification System (BCS) of the US Food and Drug Administration, drugs are classified based on two intrinsic properties that control their oral absorption: aqueous solubility and intestinal permeability (Amidon et al, 1995)
Some biopharmaceutical properties of 6MC were determined in order to increase the preclinical characterization of this promising drug
Summary
The oral route is the most common route for administration of new drugs, as it is considered the safest and most convenient. According to the Biopharmaceutics Classification System (BCS) of the US Food and Drug Administration, drugs are classified based on two intrinsic properties that control their oral absorption: aqueous solubility and intestinal permeability (Amidon et al, 1995). Knowledge of these drug properties assists in the classification of a drug in the BSC, and guides the selection of candidate drugs during the drug development process (Griffin, ODricoll, 2008).
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