Pharmacokinetic study of loprinone hydrochloride, a new cardiotonic agent, in beagle dogs.
Pharmacokinetic parameters and bioavailability of a new cardiotonic agent, loprinone hydrochloride, in beagle dogs were determined by measuring plasma levels of loprinone after intravenous bolus and oral administration. The plasma half-life after intravenous administration of loprinone varied among individuals over the range 2.65-15.40 h. The bioavailability after oral administration of loprinone as a solution was 37.1%. Effects of enterohepatic circulation on the time-course of plasma levels after intravenous administration of the drug were also studied in bile-duct-cannulated beagle dogs. The amounts of loprinone and its glucuronide excreted in bile during 8 h after administration were 25.4 and 8.6% of the dose, respectively, indicating the possibility of enterohepatic circulation. The plasma half-life in bile-duct-cannulated beagle dogs was 1.98 h. These results indicate that the variation in the half-life in beagle dogs resulted from enterohepatic circulation and that the true half-life is about 2 h. The relative bioavailability after oral administration of the drug as a powder in a capsule compared with a solution was 95.7%. In addition, the amounts of loprinone and its glucuronide excreted in bile, and the AUC of plasma level after infusion for 30 min into the portal vein in bile-duct-cannulated beagle dogs were similar to those after bolus intravenous administration. These results show that the low bioavailability reflects incomplete absorption.
Uemura
Y
Y
Tsukuba Research Laboratories, Eisai Co. Ltd., Ibaraki, Japan.
Tanaka
S
S
Ida
S
S
Yuzuriha
T
T
D000284:Administration, Oral; D000818:Animals; D001652:Bile Ducts / Q000502:physiology; D001682:Biological Availability; D002316:Cardiotonic Agents / Q000097:blood / Q000493:pharmacokinetics*; D002404:Catheterization; D004285:Dogs; D006207:Half-Life; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous / Q000662:veterinary; D011728:Pyridones / Q000097:blood / Q000493:pharmacokinetics*
D002316:Cardiotonic Agents; D007093:Imidazoles; D011728:Pyridones; C059498:olprinone