Pharmacokinetics of a new histamine H2-receptor antagonist, Z-300, in rat and dog.
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 half-life 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 alpha1-acid glycoprotein (alpha1-AG), because Z-300 bound more strongly to alpha1-AG than to albumin.
Sugimoto
T
T
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd, Saitama, Japan.
Furuta
S
S
Kawamata
H
H
Suzuki
M
M
Sano
H
H
Ito
T
T
Hirabayashi
N
N
Imamura
F
F
Matsuki
Y
Y
D000081:Acetamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007700:Kinetics; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000032:analysis; D013997:Time Factors
D000081:Acetamides; D006635:Histamine H2 Antagonists; D010880:Piperidines; D012709:Serum Albumin; C077871:Z 300