Effects of antacid and probenecid on gastrointestinal absorption and renal excretion of Y-26611 in healthy humans.
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We investigated the effects of an antacid (dried aluminum hydroxide gel, AL) and probenecid on the gastrointestinal absorption and renal excretion of Y-26611 after oral administration in six healthy male volunteers. The subjects were given 200mg of Y-26611 p. o. with or without 1.0 g of AL or 1.5 g of probenecid. The time course of plasma and saliva levels, urinary concentrations and urinary recovery of Y-26611, and its pharmacokinetic parameters were then determined. Y-26611 concentrations in the samples were measured by the HPLC method. The pharmacokinetic parameters obtained for Y-26611 were as follows: <I>C</I><SUB>max</SUB>, <I>T</I><SUB>max</SUB>, <I>T</I><SUB>1/2</SUB> and AUC<SUB>0-∞</SUB> after Y-26611 alone were 1.090 μg/ml, 1.1 h, 5.1 h and 3.821 μg·h/ml, respectively, after combined administration with AL, 0.082 μg/ml, 1.8 h, 5.9 h and 0.629 μg·h/ml, respectively, and after combined administration with probenecid, 1.090 μg/ml, 1.7 h, 4.4 h and 7.033 μg·h/ml, respectively. The levels of Y-26611 in saliva were less than 10% of those in plasma regardless of method of administration. The urinary excretion rates of Y-26611 over 24 h were 40.8%, 5.3% and 22.5% for Y-26611 administered alone, with AL, and with probenecid, respectively. Gastrointestional absorption of Y-26611 was markedly inhibited by interaction with AL. Furthermore, the effects of probenecid on the pharmacokinetic parameters of Y-26611 suggest that the urinary excretion of Y-26611 is related to secretion by the renal tubules.
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