Concentration of intrathecal 3H-labeled metrizamide in normal dog brain: age-related differences

Responses to intrathecal metrizamide in dogs were found to be age-related: Adult dogs had seizures; 7-week-old dogs appeared stuporous; 6-day-old dogs were clinically unaffected. The brain metrizamide concentrations 4, 6, and 20 hr after intrathecal injection correlated directly with the occurrence and severity of neurotoxic symptoms. Age-related differences in brain metrizamide concentration may be explained by two factors. The first is the failure of current clinical guidelines to adjust the recommended dosage of metrizamide to reflect differences among age groups in brain weight rather than body weight. This error resulted in lower doses/gram of brain weight being given to the puppies. However, the large differences in brain metrizamide concentrations among the three groups of dogs could not be explained solely by differences in the dose. A second factor, physiologic age-related differences in brain penetration, is believed to be operative. The precise nature of these differences is unclear.