Pharmacokinetics of a non-narcotic analgesic, DA-5018, in rats

The pharmacokinetics of a non-narcotic analgesic, DA-5018, were compared after single intravenous (i.v.), subcutaneous (s.c.), and oral administrations, and after multiple (seven consecutive days) s.c. administration to rats. After i.v. administration of DA-5018, 1, 2, and 5 mg kg-1, the pharmacokinetic parameters of DA-5018 were independent of the dose ranges studied. After oral administration of DA-5018, absorption of the drug from gastrointestinal (GI) tract was fast, but the extent of absolute bioavailability (F) was low; the values were 23.2, 23.0, and 27.3% for 2, 5, and 10 mg kg-1, respectively. After single s.c. administration of DA-5018, absorption of the drug from the injected site was fast and the extent of absorption was fairly good; the F values were 74.5 and 71.8% for 2 and 5 mg kg-1, respectively. The lower F values after oral administration of DA-5018 to rats could be due to degradation of the drug in rat GI tract and/or considerable first-pass effect. After i.v., oral, and s.c. administration of DA-5018, the drug had a strong affinity to the rat tissues studied as reflected in the greater-than-unity tissue to plasma ratio. After i.v., oral, and s.c. administration of the drug, the biliary and urinary excretion of unchanged DA-5018 were negligible. There was no significant difference in the pharmacokinetics or tissue distribution of DA-5018 between single and multiple s.c. administration of the drug, 5 mg kg-1, to rats, indicating that there could be no tissue accumulation of the drug after multiple s.c. administration of the drug to rats.