Toxicity of 8-Methoxypsoralen in Cynomolgous Monkeys (Macaca Fascicularis)
| Autor: | Karl K. Rozman, F. Leuschner, T. Rozman, R. Brickl |
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| Rok vydání: | 1989 |
| Předmět: |
Male
Pharmacology Time Factors Chemical Health and Safety Vomiting Nonlinear pharmacokinetics Health Toxicology and Mutagenesis Body Weight Public Health Environmental and Occupational Health Physiology Blood Pressure General Medicine Biology Toxicology Eating Electrocardiography Macaca fascicularis Immunology Toxicity Animals Methoxsalen Female |
| Zdroj: | Drug and Chemical Toxicology. 12:21-37 |
| ISSN: | 1525-6014 0148-0545 |
| DOI: | 10.3109/01480548908999140 |
| Popis: | Male and female cynomolgous monkeys were administered 0, 2, 6 or 18 mg/kg 8-methoxypsoralen (8-MOP) 3 times a week orally for 26 consecutive weeks. Dose-dependent emesis was the most sensitive indicator of 8-MOP toxicity. The lowest dose to elicit emesis was 3 x 6 mg/kg/week of 8-MOP. Among the histological findings proliferation of Kupffer cells was the only recurring observation. However, these finding as well as some hematological and serum electrolyte changes lacked a dose-response relationship. In the highest dosage group one female monkey was found in moribund condition on the 39th day of the study and was killed. Histopathological evidence indicated beginning shock as the cause of the rapidly deteriorating health of the monkey. Similar to effects in man and rats, 8-MOP displayed nonlinear pharmacokinetics in the cynomolgous monkey, saturation occurring between 3 x 2 and 3 x 6 mg/kg/week. Increased clearance of 8-MOP in the lowest dosage group after 26 test weeks was attributed to a combination of enzyme induction and saturable first pass effect. Since the plasma profile of 8-MOP at the lowest dose (3 x 2 mg/kg/week) in cynomolgous monkeys closely resembles that in humans after therapeutic doses (0.4-0.6 mg/kg) and because of other similarities (vomiting as earliest sign of toxicity, saturable first pass effect), it is reasonable to assume that chronic toxicity of 8-MOP as defined in this study is quite predictive for man. |
| Databáze: | OpenAIRE |
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