Kinetics of citalopram in test animals; drug exposure in safety studies

Abstract 1. Plasma levels of citalopram and its metabolites were assayed after single oral and intravenous doses to baboons (4 mg/kg), dogs (1, 4, 5, and 10 mg/kg), rats (8 mg/kg), and mice (24 mg/kg). Kinetic parameters were estimated. 2. Half-lives were short (estimate for baboon 3, dog 3½−8, rat 3, and mouse 1½ hours) and systemic plasma clearance high (baboon 39, dog 37-14, male rat 82, female rat 103, male mouse 87, and female mouse 116 ml/min/kg body weight). Considerable first-pass metabolism was demonstrated. 3. Drug level data were obtained in long-term safety studies in dogs (1, 3, and 8 mg/kg), rats (32 and 320 mg/kg), and mice (640 mg/kg). The high-dose citalopram level in dogs and rats exceeded that of patients by a factor of 10; the factor for mice was 40.