Comparative in vivo distribution of opiate agonists and antagonists by means of double isotope techniques.

Rats were injected with mixtures of morphine-¹⁴C and naloxone-³H and and the entry of the isotopes into the brain and various tissues was measured via combustion in a tissue oxidizer. Naloxone crossed the blood brain barrier 8–10 times faster than morphine. Increasing the dose of morphine from very low to pharmacological levels had little effect on the relative tissue distribution. Administration of naloxone at intervals after a morphine dose indicated that naloxone still enters the brain more rapidly, with most of it entering during the first fifteen minutes. Similar studies using naloxone-¹⁴C and naltrexone-³H showed that naloxone enters the brain more effectively than naltrexone. This situation is reversed in the liver, since this organ disproportionately retains naltrexone.