Pharmacokinetics of a new histamine H2-receptor antagonist,Z-300, in rat and dog |
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Authors: | T. SUGIMOTO S. FURUTA H. KAWAMATA M. SUZUKI H. SANO T. ITO |
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Affiliation: | Central Research Laboratories, Zeria Pharmaceutical Co., Ltd, 25121 Oshikiri, Konan-machi, Osato-gun, Saitama 360-0111, Japan |
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Abstract: | 1. The plasma level of Z-300 reached a maximum (Cmax) at 30?min after the oral administration of Z-300 to dog, and disappeared from the systemic circulation with a halflife of 8-9 h. The bioavailability of Z-300 was 52% after the oral administration of Z-300, 3?mg/kg. At doses ranging from 3 to 30?mg/kg, Cmax and AUC (area under the plasma concentration-time curve) were proportional to the dose. 2. The plasma level of Z-300 reached Cmax at 10?min after the oral administration of Z-300 to rat, and disappeared from the systemic circulation with a half-life of 0.8-1.6 h. The bioavailability of Z-300 was 39% after the oral administration of Z-300, 10?mg/kg, and there was a non-linear relationship between the plasma level-time profile of Z-300 and the administered dose (3-50?mg/kg). 3. The binding of Z-300 to plasma protein was 92% in man, 65% in dog and 25% in rat. It is suggested that these species differences were due to the content of α1-acid glycoprotein (α1-AG), because Z-300 bound more strongly to α1-AG than to albumin. |
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